1. PLANT/FACILITIES ENGINEERING IN THE PHARMACEUTICAL INDUSTRY

2. 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

3. ASEPTIC & STERILE FILLING
PRODUCTION
UTILITIES
OFFICE
WAREHOUSE
INFRASTRUCTURES
PHARMA
FACILITY
EXTERNAL
LABORATORIES
COLD ROOM
BIOTECH
ASEPTIC & STERILE FILLING
BUILDING
AREA
DESIGN OF FACILITIES
NEW PHARMACEUTICAL PROJECT
FUNCTION
ENGINEERING / PROCUREMENT / CONSTRUCTION / COMMISSIONING /START-UP / (VALIDATION)

4. PROJECT PHASES Conceptual Planning
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

5. 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

6. PROJECT INDICATORS Did you meet project scope?
Did you meet project timeline?
Did the project was within budget?

7. 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.

8. PREVENTIVE MAINTENANCE REQUIREMENTS
Tasks and frequency determined by:
Manufacturer’s recommendation
Historical data
Department supervisor and maintenance coordinator verifies completion of PM tasks
PM records maintained by the engineering department

9. 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

10. 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

11. DOWNTIME ANALYSIS
Sample report:

12. AUTONOMOUS MAINTENANCE
Traditional Roles
Production Operator
Maintenance Mechanic
Requisition/Place Materials 
Operate Line
Monitor Process Variables
Adjust Running Parameters
Check Product Quality
Place Maintenance Work Order
Adjust Machine Setup
Diagnose Unexpected Downtime
Perform Routine Maintenance
Perform Preventive Maintenance
Perform Shutdown Maintenance
Record Activities in CMMS
Lead Reliability Improvement Projects
Autonomous Maintenance 
Line Operator Example

13. 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

14. DMAIC Process Control Define Measure Improve Analyze Remedial Journey
Define Problem
Problem Statement
Pareto Charts
Form Team
Charter
Monitor
Process Management Plan
Control Charts
Scope Project
SIPOC Map
Train
Align w/Customer
VOC
Affinity Diagram
Standardize
Juran’s Pyramid
Flow Charting
What Data?
“Five Points of View”
Remedial Journey
Control
Define
How to Measure
Operational Def’s
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
(Create)
Analyze
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

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

16. 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

17. 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

18. REGULATORY AUDITS The Audit criteria includes: Audit approach:
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

19. 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

20. Preliminary Data

21. 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

22. 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

23. 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”

24. PAT OBJECTIVES Produce Pharmaceutical Manufacturing 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

25. PAT-TECHNOLOGIES Simple sensors Spectroscopic Physical properties
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

26. VALIDATION LIFE CYCLE

27. 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

28. 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