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

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

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’ www.fda.gov

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 www.fda.gov

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

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

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 www.fda.gov

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) www.fda.gov

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

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. www.fda.gov

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 www.fda.gov

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

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

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

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.

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

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

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

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

Thank You!