BioMedical Strategy - Regulatory Presentation
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This document provides an overview of medical device regulation in the US and EU markets. It discusses key aspects of the regulatory process including intended use, classification, clinical evidence requirements, and approval pathways such as 510(k) and PMA. Major topics covered include regulatory strategies, claim determination, risk-based classification, clinical study design considerations, and substantial equivalence evaluations.
BioMedical Strategy - Regulatory Presentation
- 1. Evolving Medical Device Regulation: US and EU Markets Orna Oz, PhD BioMedical Strategy (2004) Ltd Clinical & Regulatory Affairs Group September 2011
- 2. Medical Product Technological Solution Market Medical Need Analysis Regulatory R l t Patentability Scientific Evidence & Reimbursement Funding September 2011
- 3. Main Target Markets g EU USA September 2011
- 4. Medical Device Definition D fi i i • an instrument apparatus … implant in instrument, apparatus, implant, vitro reagent, or other similar or related article, article including a component part or part, accessory • Used for the diagnosis treatment or prevention of diagnosis, disease or condition and that • Affects the structure or function of the body • Does not achieve its function through chemical action • Is not metabolized to achieve effect September 2011
- 5. Medical Device Examples E l September 2011
- 6. US Market Food D F d & Drug Ad i i t ti Administration FDA/CDRH Ensuring that medical g devices are “reasonably” safe and effective September 2011
- 7. Food & Drug Administration September 2011
- 8. Product Life Cycle Premarket Phase Regulatory Strategy Pre IDE Quality Assurance September 2011
- 9. Regulatory Strategy • Intended use & Indications for use (Claim) • Regulatory Classification • Proposed pre-clinical Testing • Clinical Strategy (pre and post market) •Re-assess intended use and/or indications for use •Re-assess technological (engineering) approach and R&D plan •Re-assess business plan – designated product, timelines and budget Alternative approaches September 2011
- 10. Regulatory Strategy g y gy Proof of Concept US EU Regulatory Pathway Finalize discussion with Notified gy and Clinical Strategy body for Strategy Pre- IDE Verification & Quality System Q Validation Plan Poolability Clinical Study (OUS) IDE Clinical Study (US and OUS) IDE CE Mark 510(k) Clearance/PMA Approval September 2011
- 11. Regulatory Implications of Claim SPECIFICITY LEVEL 1. Identification of function Tool Claim 2. Identification of tissue type an organ system or (higher clinical Identification of a specific evidence)) organ 3. Identification of a particular disease or target population 4. Identification of an effect on clinical outcome Clinical Claim September 2011
- 12. Regulatory Implications of Claim SPECIFICITY LEVEL Tool vs. Clinical – Cardiac Pacing Devices Tool: The Frontier Biventricular Cardiac Pacing System is indicated for maintaining synchrony of the left and right ventricles in patients who……. Clinical: Cli i l The InSync model 8040 pulse generator is indicated for the reduction of the symptoms of moderate to severe heart failure (NYHA Functional III or IV) in those patients who……. September 2011
- 13. Claim / Intended Use GENERAL VS. SPECIFIC INTENDED USE The claim(s) for a device can be general or specific. When deciding the claims for the device it is important t consider not only th marketing goals i t t to id t l the k ti l but also the regulatory process. Examples of General vs. Specific Use: Skin resurfacing vs. Wrinkle removal vs Evaluation of soft tissue vs. Aid in differentiation of benign from malignant breast lesions g g Cut/coagulate soft tissue vs. Photorefractive keratectomy (PRK) for myopia September 2011
- 14. Claim / Intended Use GENERAL VS. SPECIFIC INTENDED USE September 2011
- 15. Classification Determination of Ri k D t i ti f Risk User/Pt g Mitigation Environment RISK Generic type Circumstances Claim September 2011
- 16. Classification Medical devices are divided into three regulatory classes based on the risk and level of control necessary to assure their safety and effectiveness. ff ti Risk Level •Exempt – Class I & II (SE) Low De Novo (NSE) •510(k) – Class I, II (SE) •PMA – Class III HDE High September 2011
- 17. Regulatory Routes 510(k) vs. PMA 510(k) devices must only demonstrate that there are as safe and as effective as similar h f d ff i i il device/s (predicates) already marketed SE determination Challenging the IP portfolio PMA devices must demonstrate, on their own merit, safety and effectiveness through valid scientific evidence Regulation poses less risks to IP portfolio tf li September 2011
- 18. Clinical Arena SR vs. NSR Devices For the purpose of clinical investigation Significant Risk ( ) – presents a p g (SR) p potential for serious risk to the health safety, or welfare of a subject… Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease…… Non SR (NSR) – do not pose a significant risk to the human subjects. • SR devices undergo FDA approval (IDE) prior to initiating clinical investigations in the US • Relevant to 510(k) and PMA classified devices September 2011
- 19. CDRH’s Risk Based Paradigm g Class I Class II Class III September 2011
- 20. 510(k) SE Determination A device is substantially equivalent if, in comparison to a legally marketed device it: has the same intended use; AND has the same technological characteristics as the legally marketed device, OR has different technological characteristics, and submitted information does not raise new questions of safety and effectiveness, and it demonstrates that the device is as safe and as effective as the legally marketed device. d i September 2011
- 21. 510(k) SE D t Determination i ti Ref: 2010 RAPS Annual Conference, Christy Foreman, Acting Director, Office of Device Evaluation, FDA September 2011
- 22. 510(k) SE D t Determination i ti Ref: 2010 RAPS Annual Conference, Christy Foreman, Acting Director, Office of Device Evaluation, FDA September 2011
- 23. 510(k) SE D Determination i i Ref: 2010 RAPS Annual Conference, Christy Foreman, Acting Director, Office of Device Evaluation, FDA September 2011
- 24. 510(k) SE D t Determination i ti Ref: 2010 RAPS Annual Conference, Christy Foreman, Acting Director, Office of Device Evaluation, FDA September 2011
- 25. Evaluation of the 510(k) Program ( ) g • 2009: The FDA turned to the IOM to review the 510(k) process and recommend on action it d d ti items • 2011: The IOM most critical comments: • Th current 510(k) process i fl The (k) is flawed b d based on i legislative d its l i l i foundation. • Rather than continuing to modify the 35-year-old 510(k) process, the IOM concludes that the FDA’s finite resources would be better FDA s invested in developing an integrated premarket and postmarket regulatory framework that provides a reasonable assurance of safety and effectiveness throughout the device life cycle. •Jeffrey Sh J ff Shuren, M D di M.D., director of the CDRH “ f h CDRH: “…..FDA b li FDA believes that h the 510(k) process should not be eliminated but we are open to additional proposals and approaches for continued improvement of our device review programs…….. Any major modifications made to the agency’s premarket review programs should be based on sound science and through thoughtful and transparent discussion….” September 2011
- 26. Device Approval in Europe CE M ki Marking September 2011
- 27. Relevant Authorities • Member State of the European Union is any one of the 27 sovereign states that have acceded to the European Union (EU) • Competent Authority has the authority to act on behalf of the government of the Member State to ensure that the requirements of the Medical Device Directives are transposed into National Law and are applied • The Notified Body (NB) is a private, commercial testing laboratory or certification organization approved by the y g pp y Competent Authority in the Member State in which they have their head-office to carry out some or all of the Conformity Assessment procedures in the medical device directives. September 2011
- 28. EC Directives • Medical Devices are regulated by the EC Directives: – the Active Implantable Medical Device (AIMD) Directive - 90/385/EEC – the Medical Device Directive (MDD) 93/42/EEC – the In Vitro Diagnostic Device Directive (IVD) - 98/79/EC. h I Vi Di i D i Di i / /EC – AIMD and MDD are now governed b the Amended Directive 2007/47/EC • Medical devices may be classified (risk based) as Class I, Class IIa, IIb and III • MEDDEV guidance documents September 2011
- 29. Assessment Route • Within the scope of which Directive? • Classification (The classification rules are based on different criteria such as the duration of contact with the patient, the degree of invasiveness and the part of the body affected by the use of the device). • Conformity Assessment Route (design and manufacturing inspections, manufacturing ONLY, etc.) t ) • Technical File (Contains all the relevant information to demonstrate that the product meets the Essential Requirements of the Directive) September 2011
- 30. Meeting the Regulatory Authorities September 2011
- 31. Pre Ruling FDA • Pre IDE – Regulatory strategy: regulatory classification, test plan ( p (bench test methodologies animal g studies), clinical strategy – Prior to expanding clinical trials from feasibility to pivotal phase Notified Body (NB) – Introductory meeting followed by discussions, and pre agreement on proposed regulatory plan agreement, (mainly testing, animal data, clinical evaluation) September 2011
- 32. Clinical Evidence September 2011
- 33. The Key to Market Penetration y A breakthrough technology is great but does not ensure ens re market s ccess success Regulatory approvals are meaningful milestones •In creating value for strategic agreements and funding •In entrance to the market Clinical evidence (data) is the leading force to successful market penetration and positioning September 2011
- 34. Clinical Strategy Need for premarket clinical data? US (FDA): • Yes - for a PMA route • No and Yes – for a 510(k) route EU: • Yes – Clinical evaluation (MEDDEV 2.7.1) (1) Clinical data (study/ies, experience) OR (2) Controlled systematic literature review of data reported on equivalent devices OR i l d i (3) a combination of (1) and (2) September 2011
- 35. Clinical Strategy MEDDEV 2 7 1 2.7.1 Stage 1* Stage 2 Identify clinical data from Appraisal of individual data sets • Suitability • Literature searching &/or • Clinical experience &/or • Contribution of performance • Clinical investigation and safety Generate new or additional clinical data N O Is clinical evidence Stage 3 sufficient to be able to declare Analysis of relevant data conformity with • Strength of overall evidence relevant ERs ? • Conclusions about performance and safety Y E S Produce clinical evaluation report September 2011
- 36. Clinical Strategy gy Post-market Post market . . . Study # 3 Study #2 FIM Investigational/pre-market September 2011
- 37. Hierarchy of Medical Scientific Evidence S i tifi E id Randomized Controlled Trial T i l Observational Trial Case-control Case control Cohort Descriptive study p y Physiologic study Case series Expert opinion Ref: 2010 ICI Meeting, Andrew Farb MD Interventional Cardiology Devices Branch, Office of Device Evaluation Meeting Farb, MD, Branch September 2011
- 38. September 2011
- 39. Some Common Pitfalls • Bad study design • Inappropriate selection of sites and/or investigators • Incomplete and/or inappropriate study management tools (procedures, logs CRFs…) • Using under-qualified clinical research personnel ( p (sponsor and/or site) ) • Poor compliance with GCP– not only necessary for regulatory reasons b also to reduce the company’s l but l d h ’ risk from potential adverse publicity and lawsuits September 2011
- 40. Site Selection IP Laws of Country Costs Scientific Publications Location / Market Availability Personnel & Facilities Regulatory Expected subjects eligibility subjects- September 2011
- 41. Investigator Selection Opinion Leader Availability September 2011
- 42. In Summary C Clinical & Regulatory Affairs is ca g ato y a s s about claiming and branding It is the umbrella that covers the Company act v t es o early development through activities from ea y deve op e t t oug market approval and up to post-marketing ac v es expediting market pe e a o activities in e pe g a e penetration Strategic planning is the key role for g p g y a least burdensome and valuable marketing route September 2011
- 43. Thank You!!! Moshe Aviv Tower, 34th, Floor 7 Jabotinsky Street, Ramat Gan E-mail: biomedical@ebms.co.il Tel: 03-6123281 September 2011