1. 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

2. 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

3. 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

4. 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 sub- offices.
Functional areas align to streamline FDA processes that assess and monitor drug quality.
Policy
Review
Inspection
Surveillance
Research
OPQ
‘One Quality Voice’

5. OPQ Structure Immediate Office
Director: Michael Kopcha
Deputy Director: Lawrence Yu
Office of Program and Regulatory Operations
Director:
Giuseppe Randazzo
Office of Policy for Pharmaceutical Quality
Director:
Ashley Boam
Office of Biotech Products
Director:
Steven Kozlowski
Office of New Drug Products
Director:
Sarah Pope Miksinski
Office of Lifecycle Drug Products
Director:
Susan Rosencrance
Office of Process and Facilities
Acting Director:
Robert Iser
Office of Surveillance
Acting Director:
Sarah Pope Miksinski
Office of Testing and Research
Director:
Cindy Buhse

6. 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

7. 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

8. Why is OPQ science and research needed for product quality?
Expectations of patients and caregivers on their drugs
Are safe, efficacious, and have the correct identity
Deliver the same performance as described in the label
Perform consistently over their shelf life
Are made in a manner that ensures quality
Will be available when needed

9. 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., abuse- deterrent 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)

10. 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)

11. 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:
Establishing clear, science-based standards and policies for consistent drug quality evaluation and lifecycle management;
Facilitating risk-based decision making regarding the quality of drug substances/drug products; and
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.

12. When OPQ Science and Research is Needed
Quality Assessment of Applications
Develop scientific approaches and methods to support OPQ’s evaluation of product quality and performance, manufacturing processes, and controls
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
Response to Public Health Issues
Support post-marketing quality monitoring
Address quality-related safety issues raised in adverse event investigations

13. 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

14. 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

15. 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)

16. 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.

17. 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

18. 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

19. 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

20. 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.
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

21. Thank You!