Implementing New

1

• Implementing New
• Process Analytic Technologies
• The underlying challenges
• PAT Subcommittee, June 12-13, 2002

Justin O. Neway, Ph.D. Executive Vice President,
Chief Science Officer Aegis Analytical
Corporation http//www.aegiscorp.com
2
Outline

• Background information sources
• Perceived benefits of PAT implementation
• What are the underlying challenges?

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Background Information Sources

• 15 Yrs in Process Development Mfg.
• Trained in Biochemistry Microbiology
• Worked in three Biotech/Pharma companies
• Intimate with data problems in PD and
  manufacturing
• 5 Yrs with Aegis Analytical Corporation
• Venture funded by GlaxoSmithKline, Merck, Aventis
• Invited presentations to 30 top Pharma Biotech
• Customer advisory panel requirements consortia

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Benefits of PAT Implementation

• Greater control of product uniformity
• Improved safety, quality compliance
• Shorter cycle times, batch release times
• Cost savings, supply chain stability
• Moves us towards parametric release
• Cost savings, lower inventory
• Moves us towards continuous operations
• Improved control, significant capital adjustment
• What about todays failure rates, compliance
  yield problems?

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The Quality Compliance Challenge

• US Drug products are of high quality BUT
• Increasing trend towards manufacturing problems
• Recalls, disruption of operations, drug shortages
• Negative impact on New Drug Applications (NDA)
• Low efficiency manufacturing and QA
• Slow innovation and modernization
• Why do these problems occur?
• Janet Woodcock, M.D.
• FDA Science Board Presentation
• November 16. 2001

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Data-intensive Decision-making

• Identify and control Critical Process Parameters
• Quality regulatory compliance (GMP)
• Parameter review for batch release
• Setting defensible specifications
• Investigation of atypical batches
• Manufacturing process validation
• Production trend analysis
• Annual Product Reviews (APRs)
• Process control (stability)
• Shorten process start-up/scale-up times
• Shorten trouble-shooting time/adverse trend
  reversal
• Improve process stability, productivity quality
• Improve Return on Net Assets (RONA)

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The Real Manufacturing Data Environment
The necessary data are in many separate locations
Process yield quality discrete replicate data
LIMS
PAT Instruments
Process instrument measurements discrete
continuous data
Warehouse
SCADA DCS PLCs
Operators, times, volumes, quantities discrete
replicate data
Batch Records
Material vendors, receive release dates,
equipment discrete replicate data
ERP
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Decision-making Inefficiencies

• Several weeks of manual data retrieval
• Not a priority for corporate IT, multiple data
  sources
• Spreadsheet madness
• Excel add-ins, discrete, continuous replicate
  data
• Bewildering choice of inadequate software
• Too many packages with too little real usability
• Programming required from non-programmers
• Antiquated ways to communicate results
• Tables of highlighted numbers
• Traditional 2D plots

9
The World Around Us

• Industry trends
• New instrumentation
• Cheap data storage
• Cheap computing power
• Increased enforcement of GMP
• Patent expirations
• Industry consolidation, globalization
• The technology already exists to adequately deal
  with the inefficiencies

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PAT Data Analysis Technology Example
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Batch Release Technology Example - VPS
Dissolution Rate
Coating Parameter

• Mixer
• Parameter

Dryer Parameter
API Parameter
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The Advantages of PAT

• A Good Balance - Compliance and Economics
• FDA
• Wants better compliance to ensure safety and
  efficacy
• Wants better manufacturing efficiency to lower
  drug prices
• Industry
• Wants to comply but lacks necessary software
  capabilities
• Has been building the cost of failed batches into
  pricing
• Wants to shorten cycle times to improve economics
• For this to work, the realties of the
  manufacturing data environment must also be dealt
  with

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What can we do?

• Industry
• Boost manufacturing IT spending
• Include mfg. users in budget prioritization
• Implement underlying IT infrastructure needed for
  PAT
• Vendors
• Make better software systems, work with industry
• Be honest about software capabilities
• Provide better training support
• FDA
• Continue emphasis on GMP compliance, outreach
• Take opportunities to emphasize positive PAT
  economics

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What can we do?

• PAT subcommittee
• Continue safe harbor policy implementation
• Account for additional necessary mfg.
  infrastructure
• Publicize compelling economic justification
• Account for hard costs, soft costs and social
  costs
• Sponsor industry/vendor working groups
• Define needs, develop requirements, provide
  feedback

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Conclusions Recommendations

• PAT implementation, more difficult than expected
• Requires much more than just new instrumentation
• Challenges similar to other data-intensive
  decision-making inefficiencies
• Poor data availability, inappropriate software
  systems
• PAT a unique economic incentive for quality
  compliance improvement
• A good balance between compliance and improved
  economics