ISPE-presentationSept28-2006-final

PLANT/FACILITIES ENGINEERING IN THE PHARMACEUTICAL INDUSTRY : 

PLANT/FACILITIES ENGINEERING IN THE PHARMACEUTICAL INDUSTRY

FUNCTIONS OF THE PLANT ENGINEERING DEPT : 

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

DESIGN OF FACILITIES : 

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

PROJECT PHASES : 

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

TYPES OF PROJECT : 

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

PROJECT INDICATORS : 

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

PREVENTIVE MAINTENANCE : 

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.

PREVENTIVE MAINTENANCE REQUIREMENTS : 

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

SHUTDOWN : 

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

SPARE PARTS : 

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

DOWNTIME ANALYSIS : 

DOWNTIME ANALYSIS Sample report:

AUTONOMOUS MAINTENANCE : 

Line Operator Example AUTONOMOUS MAINTENANCE

SWAT TEAMS-PROCESS IMPROVEMENTS : 

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

Slide 14: 

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

MANAGEMENT STANDARDS : 

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

TECHNICAL STANDARDS : 

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

TECHNICAL STANDARDS(continued) : 

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

REGULATORY AUDITS : 

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

ENERGY SAVING INITIATIVES : 

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

Preliminary Data : 

Preliminary Data

PROCESS ENGINEERING : 

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

STERILIZATION ENGINEERING : 

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

PAT : 

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”

PAT OBJECTIVES : 

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

PAT-TECHNOLOGIES : 

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

VALIDATION LIFE CYCLE : 

VALIDATION LIFE CYCLE

VALIDATION IN THE FUTURE : 

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

ADMINISTRATION : 

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