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FDA, Global Expectations, and
Validation Statistics
Marlène García Swider, Ph.D., CQM
Institute of Validation Technology
June 23 – 24, 2015
Philadelphia, PA
Personal Claim
This presentation is based on
journal articles written by the author and
does not reflect a position, official or
unofficial, of the FDA. Any reference to FDA information is based on public information.
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Past
Previously, one or two firms were
responsible for the entire manufacturing
of a product or they outsourced others to
help with some of the manufacture.
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Currently,
Today, the increasing demand for the
products along with the pressure to
reduce cost and increase productivity
calls for globalization.
No matter what part of the world
All imported products to U.S. are required
to meet the same standards as domestic
goods – must be pure, produced under
sanitary conditions, and contain
informative and truthful labeling in English.
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Statistics are no exception
“Where appropriate, each manufacturer
shall establish and maintain procedures
for identifying valid statistical
techniques…” – FDA Quality System Regulation (1996)
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What is Process Validation?
According to FDA, process validation is
the collection and validation of data, from
the process design stage throughout
production…
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What FDA wants?
Evidence that a process is capable of
consistently delivering quality product.
FDA depends on statistics…
to assure that batches of products meet
each appropriate specification and
appropriate statistical quality control
criteria as a condition for their approval
and release.
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FDA requires…
that statistical quality control criterial shall
include appropriate statistical quality
control criteria as a condition for their
approval and release.
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What are Statistical methods?
“Statistical methods are tools to be utilized
for better risk-based decision making in the
face of variation and uncertainty.”-
Paul L. Pluta, Ph.D.
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FDA Globalizes
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No matter where you are…
The same FDA guidance apply to all
the inspections done by the Agency
(in U.S. or any other country.)
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Globalization Influence Diagram
Outsourcing Globalization
State-of-the-art Science, Innovation and
Harmonization
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FDA Guidelines
Through experience accumulated
through the years, FDA revised the
Process Validation Guidance in 2011.
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Process Validation – 3 Stages
Process Design
Process Qualification
Continuous Process Verification
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How it is done - Example 1
Process Design
DOE
Risk Analysis (screening potential
variables)
Models of the commercial process
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How it is done - Example 2
Process Qualification
Design of facility and equipment/utilities
qualification
Process Performance Qualification (PPQ)
Intra-batch and inter-batch metrics
Comparison and Evaluation of process
measures, in-process, and final product
attributes
How it is done - More Examples
Bayesian Statistics:
Learning from evidence as it accumulates.
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How it is done - More Examples
Process Control Techniques
SPC Techniques (probability, multivariate
statistics, and statistical control charts)
Process Analytical Techniques (PAT)
Process Capability Studies
Control Charts
Comparison of CPK and CQA
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New Trends
What are others talking about…
Customized medication
Customers speak different languages
Introduction of new products while increasing
quality of care and reducing costs
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In Conclusion
Study and familiarize yourself with FDA
policies and regulation in order to comply
Network and participate on forums like this
one to keep in top of changes and trends
Inform yourself through researching
literature
Advice No. 1
Ensure that a statistician or person with
adequate training develops statistical
process control techniques.
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Advice No. 2
Develop data collection plans and
statistical methods and procedures for
measuring and evaluating process stability
and process capability
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Advice No. 3
Describe how trending and calculations
are performed and detect unintended
process variability
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Advice No. 4
Collect production data to evaluate
process stability and capability
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Advice No. 5
Understand the role of the quality unit and
review process
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Advice No. 6
Identify variability in the process and/or
signal potential process improvements
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References
FDA 2011 Process Validation Guidance
FDA, Quality Systems Approach to
Pharmaceutical CGMP Regulations, Guidance
for Industry, 2006
Case Study: Use of Statistical Process Control
to Detect Process Drift (Torbeck, 2011)
Guidance for the Use of Bayesian Statistics in
Medical Device Clinical Trials
www.fda.gov
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