the science of quality by design janet woodcock, m.d. may 19, 2004
TRANSCRIPT
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The Science of Quality By Design
Janet Woodcock, M.D.May 19, 2004
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What Science underlies the quality of Medical Products? Medical products must be mass produced
for use in healthcare settings
Product must be designed to fulfill intended use reliably
Manufacturing process must be designed to reliably produce a consistent product
Underlying science is NOT just the medical science
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Critical Path: Industrialization Dimension Product Design
Material properties of components Toxicologic properties of component Biological properties Feasibility of manufacture Characterizability Relationship of specifications to
performance Exploration of alternatives
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Critical Path: Industrialization Dimension
Process Design Reliability Robustness Amenable to feedback control Human Factors [Experts will discuss!]
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Quality by Design
Stipulate (postulate) key performance parameters early in development process
Design product & process to be robust for these parameters
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Quality by Design (cont.)
Experimentally determine sensitivity of parameters to changes in input or process or use (e.g. human factors)
Incorporate new information from clinical trials and experience
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The Science of Quality by Design
The less you know about what is important to quality, the more factors you need to control (both regulators & manufacturers)
Scientific efforts needed to identify important factors in both product and process and then to control variability in these factors
Techniques include DOE, risk management techniques, statistical process control, FEMA, & human factors analysis
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Goal: Consistent High Quality
But if you want to design quality in – how do you define quality?
Need consensus definition – regulators and manufacturers
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A Common Definition of Quality:
A product or service that meets/exceeds customer’s
needs
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Regulatory Context: Medical Product Quality Customer/market can’t easily or
rapidly evaluate critical attributes of performance (e.g., safety & efficacy) due to nature of products (“market failure”)
Much is at stake (life, health) so don’t just let market sort it out
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Regulatory Context: Medical Product Quality
Therefore, by statute, FDA stands in for the customer and establishes & enforces quality standards in the realm of “clinical performance”
Clinical performance = delivery of efficacy and safety as described in the label, derived from the clinical trials
Not aesthetics, price, other consumer-defined attributes
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Who are the Customers? Primary = people who take medicine (and
their parents, caregivers, relatives, etc) or use medical devices
Secondary = overall, public has a stakehealth professionals who prescribe and dispense medicine or medical
devices
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Regulator’s Definition of Quality
Outcome based – delivers clinical performance as expected
Surrogate = “fitness for use”
Regulators define “fitness for use” via standards promulgated and attributes regulated
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A product that is “fit for use” meets its established quality attributes
standards, for example
Purity Potency/strength Identity Bioavailability/delivery Labeling/packaging Physical performance (including
aspects that influence adherence and acceptability
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Another regulatory quality attribute: “made in compliance with cGMPs”
- Therefore -cGMP requirements should support
achieving the consensus definition of quality
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From the point of view of the customers:
An important quality metric for a pharmaceutical is availability
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Issue: How does surrogate “fit for use” relate to ultimate metric “clinical performance”?
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Relationship: Fitness for use -Clinical Performance
We generally lack information except at the extremes
“Fitness-for-use” not a complete surrogate due to lack of information
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Quality by Design: A Way Forward
Prospectively designate critical quality parameter during development (product & process)
Evaluate and refine
Create robust link between process parameter, specifications and clinical performance
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Summary
There are key scientific disciplines relevant to the development, design and control of medical products and the processes used to manufacture them
A consensus definition of quality needs to be developed
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Summary (cont.)
“Quality by Design” refers to making the link between the desired clinical performance parameters and the design & control parameters
The following talks give more in-depth examples of the scientific application of these principles