Integrating critical-to-quality ( CTQ) metrics into medical device product and process design

1. DISCLAIMER: The views and opinions expressed in this presentation are those of the author and do not represent the perspectives of any organization.

2. Integrating critical-to-quality (CTQ) metrics into medical device product and process design Presenter: Kanchana Iyer April 1-2, 2019

3. Summary • History of medical technology (in particular medical devices) • Approaches U.S. FDA has used to address scientific and regulatory challenges stemming from medical technology innovation • Integration of quality metrics into FDA oversight of medical products with examples • Conclusion and Final Thoughts

4. Question: Which amendment to the FD&C Act was unanimously authorized by the House and Senate? Safe Medical Devices Act of 1990  Food and Drug Modernization Act of 1997 Medical Device Amendments of 1992 Prescription Drug Amendments of 1992

5. Question: Which amendment to the FD&C Act was unanimously authorized by the House and Senate? Safe Medical Devices Act of 1990  Food and Drug Modernization Act of 1997 Medical Device Amendments of 1992 Prescription Drug Amendments of 1992

6. Food and Drug Modernization Act of 1997 • Nov 9, 1997: FDAMA signed by unanimous vote • Nov 21, 1997: President Clinton signed bill into law • FDA issued numerous guidance documents to address technical issues • One major goal: Improved collaboration between manufacturers and FDA

7. Next Steps • FDAMA 1997 introduced a very important objective: Improved collaboration between manufacturers and FDA • Medical device technology changes over the last two decades • FDA response to medical device technology changes

8. Quickly evolving technologies • FDAMA exempted most Class I and many Class II devices from premarket requirements • More than 1000 product codes added between 1990-2009 • Drug eluting stents (DES) is a good example of a quickly evolving technology • DES presented scientific and regulatory challenges

9. Drug Eluting Stents • 1980s: metallic stents • 1990s: rapid development of metallic stents • Restenosis rates of metallic stents were high • 2000s: introducing a drug to the stent reduced restenosis rates • 2002: introduction of FDA Office of Combination Products

10. Drug Eluting Stents • 2002 and 2003: first DES approved by FDA • Use of DES over time led to blood clots • Number of DES-related product recalls were rising • 2007: FDA advisory panel to focus on late stage thrombosis caused by DES

11. Drug Eluting Stents • Advisory panel found more than 60% off-label usage of DES • Advisory panel concluded that benefits do outweigh risks- especially against bare metal stents • Future of DES is promising

12. Precision Medicine • 1990: Human Genome project began- sequencing of all genes in human beings • 2003: full human genome sequence published • Precision medicine: tailoring treatments based on individual’s genetic makeup and lifestyle • 2017: FDA approved record number of “personalized” medicine products • 2018: FDA issued two draft guidances on Next Generation Sequencing and IVD standards

13. Medical Software • 2006: more than half of medical devices on U.S. market contained software • Software development presents new challenges for regulators • Applicable standards • Human factors • Software updates/maintenance • FDA published guidance over the last decade to provide recommendations for industry • FDA has increased its focus on integrating cybersecurity measures into premarket requirements

14. Recap… • Medical technologies quickly evolving over the last 20 years have led to scientific and regulatory challenges • FDA has analyzed data and listened to feedback from the public and devised methods to address these challenges • These approaches have required collaboration between FDA and industry • FDA has recognizes that these approaches could be better defined

15. Manufacturers Response • Manufacturers face competition and increased pressure to obtain regulatory approvals • Quality management systems (QMS) are in place to address product and process improvements • Improvement of processing and production are foundations of Quality Assurance and Quality Control

16. Question: What concept is demonstrated by the accompanying figure? • Failure mode and effects analysis  • Optimization • Root cause analysis • Critical-to-quality

17. Question: What concept is demonstrated by the accompanying figure? • Failure mode and effects analysis  • Optimization • Root cause analysis • Critical-to-quality

18. Critical-to-Quality • Developed as part of Six Sigma • Customer requirements are translated to critical-to-quality elements • Critical-to-quality elements: elements considered to be critical to determining success of a project/product/process • Identification of these elements is part of quality assurance • Due to difficulty in identification of these elements, manufacturers often use controls to catch product defects

19. Critical-to-Quality • 2011: FDA reported 70% of device recalls were due to design, material, or process failures • Utilize a proactive, CTQ management approach- this is challenging • FDA recognized that a mechanism for addressing quality requirements should be implemented

20. Case for Quality • 2011: FDA launched Case for Quality to focus more on quality • 2017: CDRH launched Voluntary Medical Device Manufacturing and product Quality Program Pilot • Uses model initially developed by Capability Maturity Model Integration (CMMI) Institute • Medical device manufacturers are able to measure their capability to product high quality, safe, and effective devices • Major objective is so FDA can modify its submission and inspection requirements based on these quality metrics

21. Case for Quality • Premarket Approval Critical-to-Quality Program • Goal: streamline premarket approval process while assuring the firm’s quality management system includes controls and critical-to-quality characteristics • Promoting quality in device design and manufacturing

22. 21st Century Cures • 2016: Signed into law by President Obama • Objective: accelerate development, innovation, and market activities for medical products • Digital Health Innovation Action Plan- reimagining of FDA’s approach to regulating digital health products • Pre-certification program: potentially replace premarket submission for certain products • FDA completed its first version of the program- will be tested by the pre-certification program participants in 2019

23. 21st Century Cures • Breakthrough Devices Program- provide patients and health care providers timely access to breakthrough devices • Speed up development, assessment, and review of these devices while preserving the requirements for premarket approval • Manufacturers can interact with FDA experts and receive feedback in a timely manner • Feb 2019: Drug eluting balloon catheter received breakthrough device designation

24. Conclusion • FDAMA 1997 introduced a goal for improving collaboration between FDA and industry • Since then, medical technology has greatly evolved leading to scientific and regulatory challenges • FDA has been cognizant of these challenges and have devised mechanisms for clarity and more recently, integrating quality metrics into assessments • Manufacturers already integrate quality metrics as part of continuous improvement activities, but should work towards integrating into design and development activities

25. Final Thoughts • We are in a very exciting time right now • Regulatory affairs professionals are being challenged by the new technologies they will have to submit to FDA • Industry needs to be responsive and proactive to keep the momentum going • From the beginning of development activities, keep regulatory requirements, quality metrics for product and processes at the forefront

26. Thank you! Questions?