Advancing Regulatory Science at the US Food and Drug Administration

Transcription

1 Advancing Regulatory Science at the US Food and Drug Administration US Food and Drug Administration EPAA Annual Conference Brussels 9 November

2 Suzanne C. Fitzpatrick, PhD, DABT Senior Science Advisor Office of the Commissioner Donald A. Prater, DVM Deputy Director (Foods), FDA Europe Office Liaison to EFSA Janice M. Soreth Deputy Director (Medical Products), FDA Europe Office Liaison to EMA 2

3 Challenges FDA faces critical public health challenges Scientific breakthroughs may transform our approach to diseases, yet research investments are not efficiently yielding new products to benefit patients Product development is increasingly costly and success rates remain low Amongst many uncertainties, failures exist in predicting toxicity despite extensive animal testing 3

4 Regulatory Science Definition: Application of science to development and utilization of new tools, standards, and approaches for assessment of medical product efficacy, safety, and quality Critical bridge between basic discoveries & new medical products. Presents opportunities to engage throughout full life cycle of products, within FDA and externally ceresearch/specialtopics/regulato ryscience/ucm pdf 4

5 Potential of Regulatory Science Science is at the heart of all FDA does, and all of our decisions, every day. Robust regulatory science is needed to enable biomedical advances, food safety, and other aspects of FDA s work. Advances in regulatory science underpin translation of cuttingedge developments into promising products for patients. 5

6 Regulatory Science at FDA: Major Pillars in Implementation Leadership to strengthen and support science and promote innovation Office of the Chief Scientist and Science and Innovation Senior Advisory Council Scientific excellence and professional development New Office of Scientific Professional Development Recruitment and retention of outstanding scientists Commissioner s Fellowship Program Mission critical applied research Collaboration and partnerships 6

7 Science/Innovation Priorities 1. Modernize Toxicology to Enhance Product Safety 2. Stimulate Innovation in Clinical Evaluations and Personalized Medicine to Improve Product Development and Patient Outcomes 3. Support New Approaches to Improve Product Manufacturing and Quality 4. Ensure FDA Readiness to Evaluate Innovative Emerging Technologies 5. Harness Diverse Data through Information Sciences to Improve Health Outcomes 6. Implement a New Prevention-Focused Food Safety System to Protect Public Health 7. Facilitate Development of Medical Countermeasures to Protect Against Threats to U.S. and Global Health and Security 8. Strengthen Social and Behavioral Science to Help Consumers and Professionals Make Informed Decisions about Regulated Products Modernizing Toxicology crosscuts and helps enable all FDA science/innovation priorities 7

8 Why toxicology? No area of science is more important for predicting product safety or assessing environmental impact Well performed toxicology studies have protected consumers from unsafe products and from contaminants Advances provide unique promise and opportunity to transform this predictive science to: bring needed products to people faster and more safely and refine, reduce, and replace animal testing 8

9 Current Toxicology Testing Many methodologies used today originated over half a century ago. Current reliance on high-dose animal studies and application of default extrapolation procedures leaves considerable uncertainty in human health risk assessment. Traditional animal studies are time-consuming, low throughput, costly and often offer limited mechanistic information. 9

10 Roadblocks to progress? Reluctance by industry and regulators alike to incorporate new technology into regulatory practice Many underlying reasons 10

11 Collaboration will be critical Roadblocks can be eliminated through collaboration International regulators, NGOs, academia, industry, and federal scientists in active dialogue will need to drive toxicology testing towards a systems-based and nonanimal approach If this collaboration succeeds, promising new tools, will revolutionize safety assessment, dramatically improving our ability to detect, understand, and manage potential risks. 11

12 Moving new science into regulation Ability of researchers today to develop biological profiling and high throughput screening methods has outpaced traditional validation approaches Current validation involves lengthy and expensive processes that require validating in vitro data against in vivo data. FDA uniquely positioned to work with academia, EPA, NIH, industry, and others to help resolve these issues and move the field forward for many reasons 12

13 New strategies needed As new safety testing evolves, new approaches to assessing these methods must also evolve. Objective, science-based approaches to determine measurement (or pathway) and evaluate methods and data relevance, quality, and reliability are required to define potential roles for new testing methods Such approaches will differ for different tests and based on their intended use; e.g. as part of screening or other algorithmic approaches vs. intended replacement of existing test 13

14 What is FDA Doing? Raising the Profile of Toxicology: Leadership and Coordination The Office of the Chief Scientist recently formed a new FDA-wide Chemical and Environmental Science Council as a focus for proactively managing a growing portfolio of cross-cutting chemical and toxicology issues and to enhance scientific and policy communication, collaboration and training across FDA and with our external partners This Council is co-chaired by the Chief Scientist and the NCTR Director and composed of both senior and junior scientists at FDA, can form task specific Working Groups, and has been engaged in information sharing and coordination for multiple issues, including alternative testing approaches, nanotechnology safety, pharmaceuticals in the environment, and endocrine disruptors. 14

15 Regulatory Science Opportunities Initial investments in toxicology should be aimed at bolstering/ evaluating most promising new technologies to improve animal and non-animal testing, and create bridges between new (often non-animal) and existing methods and human health outcomes The development and evaluation of cell lines, engineered model tissues, model organisms and systems biology and computational science approaches into high throughput systems that test for understood pathways and risks will be critical. 15

16 What is FDA Doing? Collaboration: NIH/FDA Regulatory Science Initiative FDA and NIH launched a new regulatory science grant program, including support for novel approaches for transforming toxicology An important feature of this program is ongoing FDA and NIH staff engagement with the grantees/innovators In the near future, FDA hopes to support other extramural funding opportunities for new approaches for transforming toxicology 16

17 Heart-Lung Micromachine Integrating organ on a chip microdevices to produce a Heart-lung Micromachine for real-time measures of the efficacy, bioavailability and safety of aerosol-based drugs, nanotherapeutics and other medical products on integrated lung and heart function. The microfluidic microdevice mimics the complex structural interfaces and functionalities of the alveolar-capillary interface of the living human lung. 17

18 Replacement Ocular Battery Develop and pre-validate an in vitro battery of alternative ocular irritancy assays to replace acute ocular testing using the Draize Rabbit Eye test. Uses tiered testing strategy of alternative ocular irritation assays (CAMVA, BCOP, PorCORA, PorFocal) to determine regulatory classification of a test material without the use of live animals. (RoBatt) 18

19 Collaboration: FDA Critical Path Predictive Safety Testing Consortium New drug candidates often fail late in development after significant investments have already been made. Common toxicity problems occur in the liver, kidney, or cardiovascular system. FDA and EMA engaged in a collaborative data sharing and testing effort with academia and industry, spearheaded through the Critical Path Institute identified and qualified for regulatory submission seven biomarkers for detecting drug-induced kidney toxicity in preclinical models. 19

20 Qualification Process for Drug Development Tools Qualification is a conclusion that within the stated context of use, the results of assessment with a DDT can be relied upon to have a specific interpretation and application in drug development and regulatory decisionmaking. Once a DDT is qualified for a specific context of use, industry can use the DDT for the qualified purpose during drug development, and CDER reviewers can be confident in applying the DDT for the qualified use without the need to reconfirm the DDT s utility. gulatoryinformation/guidances/ucm pdf 20

21 Critical Path Grants The Critical Path Initiative is FDA's national strategy for transforming the way FDAregulated medical products are developed, evaluated, and manufactured. Recently awarded four critical path grants- two for biomarker qualification and two for new models to assess reproductive/developmental toxicology 21

22 Alternative Model for Male Reproductive Toxicity Establish in vitro alternative model for evaluating male reproductive toxicity by using a 3-dimensional culture that resembles organs in structure & function- integrate advanced genomic approach to evaluate male reproductive toxicants 22

23 Identification of Pathways of Developmental Neurotoxicity Develop a testing strategy of combined assays to screen chemicals using aggregate brain cell cultures Identify critical pathways using a systems toxicology approach using transcriptomics & metabolomics 23

24 Collaboration: FDA/DARPA Partnership FDA has partnered with the Defense Advanced Research projects Agency to work together to facilitate innovation, promote collaboration and enhance knowledge and efficiency. First collaboration is soliciting proposals to develop in vitro platforms to predict safety, efficacy, & pharmacokinetics of drug/vaccine candidates prior to first testing in humans 24

25 Microphysiological Systems DARPA BAA Reconfigurable platform Ten or more in vitro physiological systems Able to monitor resident tissues for up to four weeks Uses human cells Commercial availability Includes plan for validating integrated platform performance $70 million over 5 years ARPA/CMO/DARPA-BAA-11-73/listing.html 25

26 NIH-DARPA-FDA Partnership NIH plans to collaborate with FDA and DARPA to develop a chip to screen for safe and effective drug therapies before testing in humans Use human cells Goal is to develop more predicative non-clinical models for drug toxicity Awards totaling $70 million Announcement published soon 26

27 NIH-DARPA-FDA Partnership Parallel programs with DARPA Developing new tools that can be used in therapeutic development Facilitate collaboration between researchers and FDA to advance the goals of both programs FDA will help determine how this new technology can be used to assess drug safety 27

28 Collaboration: Tox 21 FDA signed a memorandum of understanding with the National Toxicology Program, the Environmental Protection Agency and the National Chemical Genomics Center to participate in the Tox21" program. Some goals of Tox 21 are to: Research, develop, validate and translate innovative chemical testing methods that characterize toxicity pathways. Research ways to use new tools to identify chemical induced biological activity mechanisms. Develop models that can be used to more effectively predict how chemicals will affect biological responses. 28

29 Collaboration: Going Forward with SOT Recently FDA met with the Society of Toxicology to discuss joint partnership possibilities including: Joint Seminars on New Emerging Toxicology Models Workshops on Validation of Emerging Toxicology Models Working groups on more predictive animal/non-animal models for cardiac, renal, and hepatic toxicity 29

30 Examples of Other Recent FDA Activities to Advance Toxicology and Public Health Commissioner s Fellowship Program: multiple outstanding young scientists engaged in toxicology related projects at NCTR and FDA s product Centers; most retained after Fellowships Joint NIEHS/FDA collaborations: e.g. NTP supported work at NCTR on bisphenol-a, including novel endpoints Gulf Oil Spill response: collaboration with NOAA in developing new assays for PAHs and dispersants and in testing programs to assure seafood safety 30

31 Moving Forward Together Investments in toxicology and regulatory science can enable FDA to better protect and promote the health of people in the United States and throughout the world. New toxicology is needed to take advantage of and safely enable revolutions in 21 st century science, from personalized medicine to nanomaterials to stem cells Moving to newer methods is challenging: Collaboration is essential to define needed pathways and catalyze change 31