PLANTFACILITIES ENGINEERING IN THE PHARMACEUTICAL INDUSTRY

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PLANT/FACILITIES ENGINEERING IN THE
PHARMACEUTICAL INDUSTRY
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FUNCTIONS OF THE PLANT ENGINEERING DEPT

• Design and construction of facilities and systems
• Maintenance of facilities and systems
• Operation of system
• Environmental, Health safety
• Regulatory compliance
• Energy management
• Technology
• Validation
• Administration, supervision, organization,
  planning

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DESIGN OF FACILITIES
NEW PHARMACEUTICAL PROJECT
FUNCTION
ENGINEERING / PROCUREMENT / CONSTRUCTION /
COMMISSIONING /START-UP / (VALIDATION)
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PROJECT PHASES

• Conceptual
• Long range plan development (1-5 years in
  advance)
• Planning
• Project scope development for next year (6-12
  months in advance)
• Request for capital expenditures (RCE)
• Develop RCE documentation 2-4 months in advance
• Execution
• Immediately pre post funding
• Closeout
• Upon completion

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TYPES OF PROJECT

• New water for injection system
• Chilled water upgrade
• Clean rooms upgrade
• Installation of a second bag printer
• Optimize clave cycles
• Install thermal oxidizers
• Electrical bussway upgrade
• Upgrade hot stamp system
• Overhaul blow mold deflasher

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PROJECT INDICATORS

• Did you meet project scope?
• Did you meet project timeline?
• Did the project was within budget?

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PREVENTIVE MAINTENANCE

• New equipment or changes are added to PM program
  via VCR (validation change request)
• Master PM describes
• Equipment identification
• Frequency
• Tasks to be performed
• Master PM approved by Maintenance coordinator,
  Engineering manager, Production manager, and
  Quality manager.

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PREVENTIVE MAINTENANCE REQUIREMENTS

• Tasks and frequency determined by
• Manufacturers recommendation
• Historical data
• Department supervisor and maintenance coordinator
  verifies completion of PM tasks
• PM records maintained by the engineering
  department

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SHUTDOWN

• Include routine activity and projects
• Require project management tools
• Involve all department and contractors
• Training is critical to avoid safety issues
• Require maintenance resource availability

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SPARE PARTS

• Increased focus on better utilization of our
  stockroom dollars
• Plants are making progress in reducing the cost
  and number of spare parts in inventory
• Alternate suppliers are being identified to
  reduce the cost of parts
• In-house local machine shops are being utilized
  where possible to fabricate parts for less than
  OEM cost

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DOWNTIME ANALYSIS
Sample report
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AUTONOMOUS MAINTENANCE
Line Operator Example
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SWAT TEAMS-PROCESS IMPROVEMENTS

• SWAT teams are used in some form at all sites
• Involves Six Sigma, Cost Reduction teams and
  Maintenance Productivity teams
• Team Targets Lines based on Labor Performance,
  Material Performance, and Standard Units Produced
• Line Improvement Projects are selected based on
  Cost vs. Return just like RCE projects
• Team evaluates mechanical performance, processes
  and procedures
• Team tracks effectiveness and strives to make
  permanent fixes

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Define Problem Problem Statement Pareto Charts
DMAIC Process
Form Team Charter
Monitor Process Management Plan Control Charts
Scope Project SIPOC Map
Align w/Customer VOC Affinity Diagram
Train
Standardize Jurans Pyramid Flow Charting
What Data? Five Points of View
Define
Control
Remedial Journey
How to Measure Operational Defs Measurements
System Analysis
Anticipate Failure Mode Process FMEA
Which Units? Representative Samples Contextual
Data
(Implement)
Address Human Side Leadership Tools
Diagnostic Journey
Measure
Plot Data Time Plots Control
Charts Frequency Plots (Histo Pareto)
Improve
Plan Implementation Planning Tools
Estimate Sigma
Analyze
(Create)
Map Process Activity Flowchart Deployment
Flowchart
Anticipate Failure Mode Design FMEA
Choose Solution Priority Matrix Pugh Matrix
Focused Prob. Statement (Problem Specification)
Set Criteria Multi Voting
List Probable Causes Is vs. Is Not Fishbone/Fault
Tree (Why)
Develop Solutions Brainstorming Idea Box, etc.
Implementation Problem
Test (Verify) Causes Scatter Diagram Strat Freq.
Plots Tables
Decision Problem
Analyze Map Cycle Times Wastes
6/14/2004
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MANAGEMENT STANDARDS

• EHS Global Management
• Strategic Planning
• Self Assessment / Risk Assessment
• Business Integration
• Training and Awareness
• Communication and Information
• Performance Measures
• Assurance Review

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TECHNICAL STANDARDS

• Confined Spaces Entry
• Underground Storage Tanks
• Dangerous Goods / Hazardous Material
• Waste Facility Selection
• Machine Guarding
• Spill Prevention
• Hazardous Process
• Waste Management
• Ergonomics
• Water

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TECHNICAL STANDARDS(continued)

• Emergency Preparedness Planning
• Air Emissions
• Significant EHS Incident Reporting
• Contractor EHS Management
• Reproductive Hazard Management
• Chemical Hazard Communication
• Capital Project Review
• Occupational Health Services

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REGULATORY AUDITS

• The Audit criteria includes
• Federal Local Environmental, Health and Safety
  Regulations, Good manufacturing practices
• Audit approach
• Facility tour
• Inspections
• Employee interviews
• Documentation / records
• Site programs and procedures
• System design

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ENERGY SAVING INITIATIVES

• Steam - natural gas
• Steam trap maintenance
• Pipes and valves insulation
• More efficient equipment
• Steam pressure adjustment
• Sanitation frequency
• Boiler economizer
• Electricity
• High efficiency motors
• Equipement operation schedules
• Low consumption fluorescent lamps
• Repair of compressed air leaks

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Preliminary Data


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PROCESS ENGINEERING

• Lyophilization Equipment Engineering
• Solution Preparation and Delivery System
  Engineering
• Pharmaceutical Water Systems Engineering
• CIP (clean in place) Systems Engineering
• SIP (steam in place) Systems Engineering
• Utility Systems Engineering
• Automation Engineering Design
• Filtration Selection Qualification Support
•  

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STERILIZATION ENGINEERING

• Terminal Sterilization of Final Product (Steam,
  Gamma, ETO)
• Sterilization of Commodities (Steam, Dry Heat,
  Gamma, ETO)
• Sterilization of Aseptic Filling Equipment
  (Steam, VHP, Dry Heat)
• Sterilization Cycle Development
• Sterilizer Equipment Design
• Sterilizer Tray/Rack Design
• New Product Submission Generation and Support

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PAT

• Systems for analysis and control of
  manufacturing processes based on timely
  measurements of critical quality parameters and
  performance attributes of raw materials and
  in-process products, to assure end-product
  quality at the completion of the process

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PAT OBJECTIVES

• Produce
• The right quality
• In the shortest time
• At the lowest cost
• Predictable fashion
• Pharmaceutical Manufacturing
• Does not always meet all criteria
• Efficiency is lower than comparable industries
• Lots of room for improvement but improvement was
  almost discouraged

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PAT-TECHNOLOGIES

• Simple sensors
• pH, temperature, pressure, etc
• Spectroscopic
• Near-IR, Imagers, Mid-IR, Raman, UV-Vis, etc
• Physical properties
• Particle size and shape, thermal effusivity,
  acoustics, etc
• Classical analytical techniques
• HPLC, GC, LOD, etc

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VALIDATION LIFE CYCLE
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VALIDATION IN THE FUTURE

• Shift to continuous validation concepts from
  up-front 3 batch concept (this comes with PAT)
• Increased usage of Commissioning activities and
  documentation to reduce IQ/OQ activities
• Focus validation efforts on product quality
  attributes
• Increased usage of documented Risk Assessments
  to streamline the validation testing

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ADMINISTRATION

• Preparation of plant/facilities budget
• Management of capital projects and expenditures
• Support production goals
• Solicitation, preparation and administration of
  contracts
• Contracting and overseeing the activities of
  various contractors and consultants
• Maintenance of current as built drawings
• Hiring and coaching of the engineering employees
• Supervision of employees
• Maintain appropriate training and certification