Facility Design for Sustainable Global Compliance

ISPE-CCPIE CHINA CONFERENCE 2010

October 26-29 2010 Beijing

New Facility & Process Strategies

Facility Design for

Sustainable Global Compliance Brian White

Manager of Business Development

CDI-Life Sciences


New Facility & Process Strategies

Today’s Pharmaceutical Industry is increasingly driven by Cost Pressure.From consumers (people, governments, insurers)From a growing list of qualified global competitorsFrom rising costs of resources (energy, labor, material)

Powerful Tools to fight Cost Pressure:Lean ManufacturingQuality by DesignSustainable Design


New Facility & Process StrategiesLean Manufacturing

Lean Manufacturing.Production Practice that recognizes that expending any resource toward any goal that does not add value is wastefulValue is defined as any action or process that the customer would be willing to pay for.Lean is a set of tools that help to eliminate wasteValue Stream Mapping (process flow, man/material flow)Kan-Ban (pull systems)Poko-Yoke (error proofing)

Lean is Cost Reduction through the Elimination of Waste


New Facility & Process Strategies▪Quality by Design

Quality by Design.

•The belief that “Quality can be Planned” and that most “Quality problems relate to the way that quality was planned”.

•Quality by Design principles have been used to advance product and process quality in every industry, and particularly the automotive industry.


New Facility & Process Strategies - Quality by Design

Quality by Design.

•Recently has been adopted by the U.S. Food and Drug Administration (FDA) as a vehicle for the transformation of how drugs are discovered, developed, and commercially manufactured.

•This FDA imperative is best outlined in its report “Pharmaceutical Quality for the 21st Century: A Risk-Based Approach.”


New Facility & Process Strategies - Sustainable Design

Sustainable Design.

•Sustainability is improving the quality of human life while living within the carrying capacity of supporting eco-systems


New Facility & Process Strategies - Sustainable Design

• Sustainable Design Renewable

Materials of Construction

Efficient Systems Minimizing Waste Maximize Recovery


Case StudyConfidential Client, Southern China

Highlights New Oral Dosage Manufacturing Facility Redevelopment zone (brown-field site) Quality by Design

Impact Assessment with Preliminary Design to Identify Critical Systems

Risk Analysis for Critical Systems


Case Study Confidential Client, Southern China

Project Team - The Client US Based Firm bringing…

familiarity w/Formulation Manufacturing Expertise QA/QC & Regulatory Requirements Marketing & Distribution Chinese JV Partner Financing & Construction Site Key site-support staff



Project Team – Design & Construction Economic Design Solution US Engineer – CDI Life Sciences

Brings GMP expertise Process & Facility Expertise in Pharmacutical

Manufacturing Coordinate FDA review of design basis Conceptual Design through BOD Procurement Support for Critical Process Systems



Project Team – Design & Construction China Engineer & Constructor – Maison Worley Parsons

Detail Design – Local Expertise Procurement & Construction Management Qualify Local Suppliers & Contractors (International

Grade) Coordinate Government Submittals (PEP)


Case StudyConfidential Client, Southern China

Project Approach Lean Manufacturing – Value Stream Mapping

Manage Adjacencies from a Lean Perspective Material & Personnel Flow Analysis Reduce low-value movement of materials & personnel

Quality by Design Manage Adjacencies - reduce risk of contamination Impact Assessment after Preliminary Design Risk Analysis

Sustainability Minimizing Classified Space – (energy savings) And Maximizing Adjacencies



Site Master-Plan



Floor-Plan



Material Flow



Personnel & Gowning Flow



Equipment & Waste Flow


Case Study – Confidential Client, Southern ChinaMinimize Classified Space


Case Study – Confidential Client, Southern China

Project Approach – Lean Considerations These Studies at the Conceptual/Preliminary Phase Meet

Lean Objectives by eliminating waste. Wasted Movement - movement of materials &

people can be minimized by analyzing Material and Personnel Flows and organizing the facility to maximize adjacencies

Transport - moving products that is not actually required to perform the processing can be minimized by employing an MRP System assures that the correct materials are available in the correct quantities at the correct time



Project Approach – Lean Considerations Inventory - all components, work-in-process and

finished product not being processed The customer does not want to pay for inventory

carrying costs as such a major lean objective is to minimize inventories (raw material, work-in-process or WIP, finished goods)

Again an MRP system is used to minimize excess inventory

Waiting - waiting for the next production step (a type of WIP)

Overproduction - production ahead of demand (can be WIP or finished goods)



Project Approach – Lean Considerations Motion - people or equipment moving or walking more

than is required to perform the processing Managed in the design process by improving

adjacencies Over Processing - resulting from poor tool or product

design creating activity Includes effort expended producing better quality

than required to meet specifications Managed in the design process by specifying

appropriate processes, equipment and systems Defects - the effort involved in inspecting for and fixing

defects


Quality by Design - Impact Assessment

• The ISPE Commissioning Guide considers the Impact Assessment

as “one of the most important activities in defining the

Commissioning and Qualification scope of a project.” • The Impact Assessment identifies the various systems: process,

process support, utility and facility and miscellaneous equipment in a

manufacturing facility and determines if the operating, controlling,

alarming or failure of a system or an equipment component of that

system has an impact on product quality. • Of special concern is identifying those systems that have a Direct

Impact on quality and the equipment items within those Direct Impact

systems that should be considered Critical Components of the

manufacturing facility.



• Considering…• Operation• Control• Alarm• Failure

• To assign impact on product quality as either • Direct• Indirect• No Impact

• Evaluating Systems including• Process• Process Support• Utility & Facility• Miscellaneous

Step-1: Impact Assessment



• Direct Impact Systems• Process Equipment• Critical Utilities



• Indirect Impact Systems• Air-Handlers• Utility Systems

• No Impact• General

Heating/Cooling• Office / Lab Equipment• Waste Treatment



• For direct impact systems• Identify critical components

• Assign validation requirements• Commissioning all systems: Direct, Indirect, None• Qualification for systems w/Impact: Direct & Indirect• PQ: Direct Impact Systems


• Built Upon Equipment List



• The Value of the Impact Assessment • Defines limit of full validation (usually less than 100%)• Defines subjects of risk analysis (usually critical systems or

components only)• Documents validation requirements and their basis



Quality by Design - Risk Analysis

• Underlying Documents• ICH Q8• ICH Q9• ASTM E2500-07• Impact Assessment

• Analysis Objectives• Focus on direct impact components • Correlate risk directly to product

integrity or patient health• Establish or vindicate design

requirements

Step-2: Risk Analysis



• Risk Methodology• Modified FMECA (Failure Mode, Effects and Criticality Analysis) Method

• Risk = Severity x Frequency x Anticipation



• Severity is Science-Based• Design space sets operating

limits

• Critical process parameters affect quality

• Consequences of straying outside design space

• Quality effects on patient health



• Frequency is Engineering-Based• F – Value = Frequency of

Failure

• Influences equipment selection


• Anticipation is Engineering-Based• A – Value = Anticipation of

Failure

• Influences control selection

• F x A, Not S, is Engineering-Based




• Worksheet aids analysis• One for each direct impact system record of

• Selected critical process parameters• Design spaces• Consequences on product quality severities

• Recommends• Allowable F-Values• Allowable A-Values

• Direct results• No prioritization required

• Work within allowable F - & A - Values



• Value of the risk analysis • Early identification of design requirements

• Minimizes over-design• Minimize re-work due to under-design


Summary

• For all New Facilities and Major Renovations:• Manufacturers must consider the benefits of designing a facility

to meet Global Regulatory Expectations (SFDA, FDA, EMEA)• And the potential Savings afforded by QbD, Lean and a Risk

Based Approach to Validation.


About The Presenter

• Brian White Brian White is Manager of Business Development for CDI-Life Sciences. He has over 20 years of experience

working in various technical, sales and marketing roles supporting facilities, equipment, systems and services for the pharmaceutical & biotech industry and the broader healthcare market. Experience includes the design, construction, installation, commissioning and validation of process and utility systems. He is active at the regional and international level of ISPE (International Society for Pharmaceutical Engineering) and is currently the VP of Programs for the Delaware Valley Chapter.

• About CDI - CDI-Life Sciences is a full-service engineering group supporting the entire life cycle of a client’s pharmaceutical or biotech production and/or research and development facility from initial concept to construction and qualification. CDI-Life Sciences’ professionals have expertise in the design, construction and validation of a diverse array of Life Sciences facilities, including API, Biologics, Vaccines, Sterile Liquids, Oral Solid Dosage manufacturing and R&D facilities. CDI-Life Sciences has extensive experience performing work that complies with USFDA, EU and other worldwide regulatory agencies.

• About MWP – MaisonWorleyParsons is the largest international EPC & EPCM Contractor in China, serving Pharmaceutical, Oil & Gas,

Refining, Chemicals, Power, Infrastructure & Environmental sectors. With major offices in Beijing, Shanghai, Tianjin, Lianyungang, Nanjing and Shenyang, MaisonWorleyParsons has successfully executed over 300 projects in the past 10 years and maintains a remarkable record of more than 48 million safe field man-hours without a single lost time injury in China.