PLANT/FACILITIES ENGINEERING IN THE PHARMACEUTICAL INDUSTRY.

PLANT/FACILITIES ENGINEERING IN THE PHARMACEUTICAL

INDUSTRY

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

NEW PHARMACEUTICAL PROJECT

ENGINEERING / PROCUREMENT / CONSTRUCTION / COMMISSIONING /START-UP / (VALIDATION)

PRODUCTION UTILITIESOFFICE WAREHOUSE

INFRASTRUCTURES PHARMAFACILITY

EXTERNALINFRASTRUCTURES

LABORATORIESCOLDROOM

BIOTECHASEPTIC &

STERILE FILLING

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

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

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

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

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

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

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

Sample report:

Traditional Roles

ProductionOperator

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

Line Operator Example

AUTONOMOUS MAINTENANCE

Autonomous Maintenance

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

DefineDefine

MeasureMeasure

AnalyzeAnalyze(Create)(Create)

(Implement)(Implement)

ControlControl

Deci

sion

Pro

ble

mD

eci

sion

Pro

ble

m

Imple

menta

tion

Pro

ble

mIm

ple

menta

tion

Pro

ble

m

Define ProblemProblem StatementPareto Charts

Form TeamCharter Scope Project

SIPOC Map

Align w/CustomerVOCAffinity Diagram

What Data?“Five Points of View”

How to MeasureOperational Def’sMeasurements System Analysis

Which Units?Representative SamplesContextual Data

Plot DataTime Plots & Control ChartsFrequency Plots (Histo & Pareto)

Estimate Sigma

Map ProcessActivity FlowchartDeployment Flowchart

Focused Prob. Statement(Problem Specification)

List Probable CausesIs vs. Is NotFishbone/Fault Tree (Why)

Test (Verify) CausesScatter DiagramStrat Freq. PlotsTables

Analyze MapCycle TimesWastes

Develop SolutionsBrainstormingIdea Box, etc.

Set CriteriaMulti Voting

Choose SolutionPriority MatrixPugh Matrix

PlanImplementation

Planning Tools

Address Human Side

Leadership Tools

Anticipate Failure Mode

Process FMEA

StandardizeJuran’s PyramidFlow Charting

Train

MonitorProcess Management PlanControl Charts

6/14/2004

DMAIC ProcessDMAIC Process

Anticipate Failure Mode

Design FMEA

ImproveImprove

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 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)

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

• 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

•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

Monthly Consumption (m3)

0

50000

100000

150000

200000

250000

300000

350000

400000

Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

Month

m3

2005 2006

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

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

“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

• 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

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 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

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