Transcript Why is OPQ science and research needed for product quality?

OPQ Science and Research for
Supporting Drug Quality Evaluation,
Standards and Policy
Michael Kopcha, Ph.D., R.Ph.
Director
Office of Pharmaceutical Quality
CDER/FDA
The National Institute for Pharmaceutical Technology and Education Conference
Scientific Design of Pharmaceutical Products:
21st Century Methodologies, Technologies & Perspectives
October 3, 2016
Outline
• Office of Pharmaceutical Quality (OPQ)
• What is OPQ Science and Research?
• Why is OPQ science and research needed for
product quality?
• When is OPQ science and research needed for
product quality?
• How can NIPTE help to advance drug quality
through science and research?
• Summary and Conclusions
www.fda.gov
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Desired State
“A maximally efficient, agile, flexible pharmaceutical
manufacturing sector that reliably produces high quality drugs
without extensive regulatory oversight”
Assure that quality medicines are available for the American public
www.fda.gov
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Office of Pharmaceutical Quality
• To keep pace with increasing
product complexity, OPQ is
organized around discipline and
expertise.
• The review function matrices
across OPQ allow for enhanced
interactions, communication,
and consistency among suboffices.
• Functional areas align to
streamline FDA processes that
assess and monitor drug
quality.
www.fda.gov
Policy
Research
Review
OPQ
‘One Quality
Voice’
Surveillance
Inspection
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OPQ Structure
Immediate Office
Director: Michael Kopcha
Deputy Director: Lawrence Yu
Office of Biotech
Products
Director:
Steven Kozlowski
Office of Program and
Regulatory Operations
Office of Policy for
Pharmaceutical Quality
Director:
Giuseppe Randazzo
Director:
Ashley Boam
Office of New Drug
Products
Director:
Sarah Pope Miksinski
Office of Surveillance
Acting Director:
Sarah Pope Miksinski
www.fda.gov
Office of Lifecycle
Drug Products
Office of Process and
Facilities
Director:
Susan Rosencrance
Acting Director:
Robert Iser
Office of Testing and
Research
Director:
Cindy Buhse
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OPQ Objectives
• Provide seamless integration of
review, inspection, surveillance,
and research across the product
lifecycle
• Assure that all human drugs meet
scientifically-sound quality
standards to safeguard clinical
performance
• Enhance science- and risk-based
regulatory approaches
• Transform product quality
oversight from a qualitative to a
quantitative, expertise-based
assessment
• Encourage development and
adoption of emerging
pharmaceutical technology
www.fda.gov
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Defining OPQ Science and Research
Science = any testing and
scientific investigation of
methods and data
Research = proactive science
for the development of tools
and approaches for
evaluating drug quality and
performance
www.fda.gov
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Why is OPQ science and research
needed for product quality?
Expectations of patients and caregivers on their drugs
Are safe,
efficacious,
and have the Deliver the
same
correct
Perform
performance
identity
as described consistently
over their
in the label
shelf life
www.fda.gov
Are made in
a manner
that ensures
quality
Will be
available
when needed
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Why is OPQ science and research
needed for product quality?
Increasing complexity of products,
manufacturing processes and controls
• Enhancing the safe use, performance,
and/or availability of products enabled
by new scientific knowledge (e.g., abusedeterrent formulations)
• Using new regulatory programs (e.g.,
biosimilars)
• Enhancing manufacturing and product
quality through the development and
adoption of emerging technologies (e.g.,
continuous manufacturing)
www.fda.gov
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Why is OPQ science and research
needed for product quality?
Change in clinical development
• Accelerated application programs
(e.g., breakthrough therapies)
• Increasing needs for treatments
targeting small patient populations
(e.g., rare diseases and personalized
medicine)
• Need for transformation in
manufacturing techniques and
platforms (e.g., flexible and agile
manufacturing)
www.fda.gov
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Why is OPQ science and research
needed for product quality?
Science and research enable and inform effective
drug quality review, facility inspection and
surveillance by:
1. Establishing clear, science-based standards and policies
for consistent drug quality evaluation and lifecycle
management;
2. Facilitating risk-based decision making regarding the
quality of drug substances/drug products; and
3. Being responsive to public health, industry, and
reviewer/investigator needs for increased scientific
understanding of quality’s effects on the safety and
efficacy of drug products.
www.fda.gov
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When OPQ Science and Research is
Needed
1. Quality Assessment of Applications
– Develop scientific approaches and methods to support OPQ’s
evaluation of product quality and performance, manufacturing
processes, and controls
2. Standards, Guidance, and Policy Development
– Develop methods and generate data to support guidances
– Establish standards for product quality and performance
– Establish standards for pharmaceutical equivalence of generic
products
3. Response to Public Health Issues
– Support post-marketing quality monitoring
– Address quality-related safety issues raised in adverse event
investigations
www.fda.gov
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1. Quality Assessment of Applications
• Develop a systematic approach to product
development to aid effective assessment of scale-up
approaches for commercial production
– Evaluate complex batch processes for high‐risk APIs and solid
oral dosage forms across scales
• Build knowledge platform to aid effective quality
assessment of emerging manufacturing technology
– Develop process modeling and simulation tools to facilitate
quantitative initial risk assessment for product quality
www.fda.gov
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1. Quality Assessment of Applications
Develop fingerprint-like analytical approaches to
characterize chemical structure of complex molecules or
biosimilars
• Assess chemical equivalence amongst complex molecules that are
heterogeneous (e.g., heparin, enoxaparin and glatiramer acetate).
• Develop chemometric methods in comparing multivariate analytical
data of complex drug products (e.g., enoxaparin and glatiramer
acetate).
LC-MS chromatographic alignment of glatiramer acetate samples
www.fda.gov
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2. Standards, Guidance and Policy
Development
General Guidance
• General Principles for Evaluating the Abuse Deterrence of Generic
Solid Oral Opioid Drug Products
Product Specific Draft Guidance
• Conjugated Estrogens - developed advanced analytical methods and
established scientific standards for demonstration of pharmaceutical
equivalence (drug substance sameness)
Standards/Guidelines
• Clinically-relevant specification (e.g., biorelevant dissolution)
• Best practices for dynamic light scattering analysis
Policy
• Synthetic (generic) vs. recombinant peptides (RLD)
www.fda.gov
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3. Responses to Public Health
• Analytical support for Media/Medwatch/Consumer complaint
investigations
− Methylphenidate in-equivalence: in vitro testing supported the decision
to change the rating of generic products
− Heparin contamination and quality: new test methods were development
for root cause determination and use in on-going quality testing and
modernize USP Heparin Monograph
• Analytical support for surveillance testing to determine the
quality of drugs manufactured in different countries
• Proactive actions to address potential quality issues
 Standard testing development to assess the quality of generic products
intended for use in NG tubes with respect to their potential blockage
during the NG tube administration
 Research to understand and quantify adhesion and cold flow in
transdermal products.
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How Can NIPTE Assist Pharmaceutical
Community?
• Establish fundamental understanding of formulations
(e.g., API and excipient properties and release
mechanism), processes (e.g., batch unit operations at
different scales), and their control strategy (e.g., PAT
and analytical methods) to aid establishment of
knowledge platform in a public domain
• Train and develop future employees for the
pharmaceutical industry and FDA
• Serve as a driving force for innovation: “What is next
for pharmaceutical technologies?”
• Help to establish guidelines for emerging
pharmaceutical technologies
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How Can NIPTE Assist OPQ?
• Complement CDER’s own laboratory capabilities
to address agency priorities through science and
research
• Help to address emerging quality issues
• Help to develop a formal risk assessment of
various combination of formulations, processes
and control strategies for regulatory purposes
• Provide training
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Examples of FDA-NIPTE Projects
• Complex dosage form and formulation
• In vivo studies supporting redefining
transdermal strength and establishment of
clinically relevant dissolution specification
• Quality by design for manufacturing scale up
• Process analytical technologies
• Pharmaceutical process modeling
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Summary and Conclusions
OPQ’s science/research function is key to advancing CDER’s needs
for pharmaceutical quality and performance of products and
advancing CDER’s Strategic Priorities.
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Improves FDA’s capacity for evaluating and monitoring drug
quality and performance
Helps modernize current pathways or specify new pathways
Works to address mission critical issues as needed
Maintains a state of ‘research readiness’ that anticipates future
needs and allows for rapid response
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Thank You!