Thank Your for Attending Arden House 2004

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Thank Your for Attending Arden House 2004

• Ajaz S. Hussain, Ph.D.
• US Coordinator/Chairperson

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At the end of this conference..

• Attendees should gain a sufficient level of
  understanding of the terms used to describe the
  desired state of pharmaceutical development and
  manufacturing to
• Improve the current articulation of the desired
  state
• Be able to connect-the-dots (e.g., process
  understanding - risk to quality risk based
  regulatory requirements such as CMC specs and
  validation)
• Contribute to within company dialogue and debate
  on the future direction of these initiatives and
  assist in enhancing the utility of pharmaceutical
  science and engineering principles
• Identify areas of further self-study of new
  principles and tools (e.g., multivariate
  statistics, risk assessment tools such as FMEA,
  knowledge management tools)
• Identify future work/activities to shape the
  evolution and realization of these concepts

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Desired State
http//www.fda.gov/cder/gmp/21stcenturysummary.htm

• Product quality and performance achieved and
  assured by design of effective and efficient
  manufacturing processes
• Product specifications based on mechanistic
  understanding of how formulation and process
  factors impact product performance
• Continuous "real time" assurance of quality

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Desired State
http//www.fda.gov/cder/gmp/21stcenturysummary.htm

• Regulatory policies tailored to recognize the
  level of scientific knowledge supporting product
  applications, process validation, and process
  capability
• Risk based regulatory scrutiny relate to the
• level of scientific understanding of how
  formulation and manufacturing process factors
  affect product quality and performance, and
• the capability of process control strategies to
  prevent or mitigate risk of producing a poor
  quality product

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                          Ignoring the Long Run
Effects of Feedback Can Lead to Unintended
Consequences
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Arden House 2004

• Builds on Arden House 2003 Process Analytical
  Technology (PAT)

PAT Process Understanding
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Adding PAT to FDAs Alphabet Soup
PAC? - Post Approval Change
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A Historical Note on Quality Lurching from Fad
to Fad?

• Sampling Plans (50s)
• Zero-Defect Movement (60s)
• ISO-9000 (80s)
• QS-9000
• Malcolm Baldrige Award
• European Quality Award
• Total Quality Management
• Six Sigma
• The Ultimate Six Sigma - The Big Q

PAT
K. R. Bhote and A. K. Bhote. World Class Quality
(2000) ISBN 0-8144-0427
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BCS, PAT You want to do WHAT?!?
PAT
Regulatory Department
RD
Manufacturing
Formulations Department
Pharmacokinetics Department
Regulatory Department
BCS
Jack Cook, Pfizer.
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A Perspective on PAT One piece of the puzzle

• Vision 2020 - I can see clearly now
• Quality performance by design Continuous
  real time monitoring of quality
• Specifications based on mechanistic understanding
  of how formulation and process factors impact
  product performance
• High efficiency and capacity utilization
• Science based regulatory decisions focused on
  product and process quality

http//www.fda.gov/ohrms/dockets/ac/01/slides/3804
s1_02_hussain.ppt
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PAT Teams ORA, CDER CVM
PAT Steering Committee Doug Ellsworth,
ORA/FDA Dennis Bensley, CVM/FDA Mike Olson,
ORA/FDA Joe Famulare, CDER/FDA Yuan-yuan Chiu,
CDER/FDA Frank Holcomb, CDER/FDA Moheb Nasr,
CDER/FDA Ajaz Hussain Chair, CDER/FDA
PAT Review - Inspection Team Investigators Rober
t Coleman (ORA/ATL-DO) Rebecca Rodriguez
(ORA/SJN-DO) Erin McCaffery (ORA/NWJ-DO) George
Pyramides (PHI-DO) Compliance Officers Albinus
DSa (CDER) Mike Gavini (CDER) William Bargo
(CVM) Reviewers Norman Schmuff (CDER) Lorenzo
Rocca (CDER) Vibhakar Shah (CDER) Rosario
DCosta (CDER) Raafat Fahmy (CVM)
PAT Policy Development Team Raj Uppoor,
OPS/CDER Chris Watts, OPS/CDER Huiquan Wu,
OPS/CDER (Ali Afnan, OPS/CDER)
PAT Training Coordinators John Simmons, Karen
Bernard and Kathy Jordan
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Product and Process Quality Knowledge
Science-Risk Based cGMPs
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Regulatory Violations and Enforcement
Good Citizens
FDA Focus on High Risk
Kagan and Scholz. Perspectives on Regulation
Law, Discretion, and Bureaucratic behaviour, May
1980.
Low Risk