ACPS Manufacturing

Subcommittee
Update – 10/21/03
Judy P. Boehlert, Ph.D.
Chair
 May 2003 Meeting
• May 21-22
– Pharmaceutical cGMPs for the 21st Century: A
Risk-Based Approach
– Transition from Process Analytical
Technologies (PAT) Subcommittee to
Manufacturing Subcommittee
– Update - Regulatory Approaches Regarding
Aseptic Manufacturing
 May 2003 Meeting
• “Desired State” presented by FDA:
– 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
 May 2003 Meeting
• Desired State, continued:
– Regulatory policies tailored to recognize the
level of scientific knowledge supporting
product applications, process validation, and
process capability
 May 2003 Meeting
– Risk based regulatory scrutiny relate to the:
• level of scientific understanding of how formulation
and manufacturing process factors affect product
quality and performance
• the capability of process control strategies to
prevent or mitigate risk of producing poor quality
product
 Meetings to Date
• September 17
– Quality by Design
– Relationship between Quality by Design and
Risk Based Regulatory Scrutiny

Committee was asked to address each of these

topics
 Questions to the Committee
• Quality by Design
– Articulate a clear description of the term
Quality by Design
– Identify the type of information and knowledge
most useful to assess Quality by Design
– Regulatory approach for assessment of
pharmaceutical development knowledge to
maximize its value without impacting drug
development
 Quality by Design
• General agreement that:
– Quality by Design is a dynamic process starting in
product development and continuing to post-
approval
– Need to identify critical control points
– Need to understand boundaries of the process and
basic failure modes in terms of safety and efficacy
– Need to understand process variability
 Quality by Design
• General agreement:
– Need to assess robustness of the critical control
points
– Focus on either development or post-approval
has advantages and disadvantages
 Quality by Design
• Quality by Design: a systematic process of
achieving desirable quality by a careful and
methodical scrutiny of all the attributes that
go into characterizing quality, from the
inception of a product to its end use,
involving all its stakeholders (the patient,
the manufacturer, the physician and the
regulator)
 Questions to the Committee
• Relationship between Quality by Design &
Risk Based Regulatory Scrutiny
– FDA sought subcommittee recommendations
on ways to link the concept of risk based
regulatory scrutiny to quality by design
 Risk Based Regulatory Scrutiny
• Concept: Use process understanding as a
means for Quality by Design.
• PAT: A high level of process understanding
defined as being able to understand the
change and impact, and thereby make a risk
assessment
 Risk Based Regulatory Scrutiny
• General agreement: less burdensome
change management system based on
development information provided, as well
as testing protocol, is needed to qualify
change
• Use pharmaceutical development
information to manage post-approval
change
 Risk Based Regulatory Scrutiny
• New culture “Information sharing”
between FDA and manufacturers
• Submission of pharmaceutical development
reports
– Aids in post-approval changes
– Helpful in training FDA personnel