![FDA Warning Letter (1)
Between July 26 and August 24, 2010, Thomas R. Beilke, representing the
U.S. Food and Drug Administration (FDA), conducted an investigation of your
former practice
practice.
During the course of the inspection, Mr. Beilke met with you to
review your conduct of a clinical investigation (Protocol (b)(4), titled
"(b)(4)") performed for (b)(4). You were the investigator for this clinical
investigation between March 2008 and March 2009……..
From our review of the establishment inspection report and
the documents submitted with th t report, we conclude th t
th d t b itt d ith that t l d that
you did not adhere to the applicable statutory requirements
and FDA regulations governing the conduct of clinical
investigations.
1. You failed to ensure that the investigation was conducted
according to the signed investigator statement, in that you failed to
g g g , y
personally conduct or supervise the clinical investigation [21 CFR
312.60].
2. You failed to ensure that the investigation was conducted
acco di g to the investigational plan [21 CFR 312 60]
according i estigatio al la 312.60].
December 2011](https://image.slidesharecdn.com/biomedicalstrategyworkshoppresentations-13236109105882-phpapp02-111211074921-phpapp02/85/BioMedical-Strategy-Medical-Devices-Workshop-Presentations-50-320.jpg)
![FDA Warning Letter (2)
This Warning Letter is to inform you of objectionable conditions observed
during the Food and Drug Administration (FDA) inspection conducted at
Orthocon, Inc.
Orthocon Inc ...
The purpose of this inspection was to determine whether activities as
sponsor of the clinical studies (b)(4) and (b)(4) complied with
applicable federal regulations.
This letter also requests prompt corrective action to address the violation
cited and discusses your written response dated September 23 2010 to the
23,
noted violation. Failure to secure the investigator’s compliance. [21
CFR 812.46(a)]: Sponsors are responsible for monitoring and
ensuring compliance of clinical investigators participating in the
investigation.
A sponsor who discovers that an investigator is not complying with the
signed agreement the investigational plan applicable FDA regulations or
agreement, plan, regulations,
any conditions of approval imposed by the reviewing IRB or FDA shall
promptly either secure compliance or discontinue shipments of the device
to the investigator and terminate the investigator’s participation in the
investigation.
December 2011](https://image.slidesharecdn.com/biomedicalstrategyworkshoppresentations-13236109105882-phpapp02-111211074921-phpapp02/85/BioMedical-Strategy-Medical-Devices-Workshop-Presentations-51-320.jpg)
![Principles of Law-VII
• “A device is ‘substantially equivalent’ if it has
the same intended use and the same
technological characteristics as those of the
existing device.
• “Thus, the 510(k) submission compares the
accused product, Baxa's compounders, with
the commercial embodiment of the ‘010
patent, Clintec's compounders. “ [I]t is error for
a court to compare in its infringement analysis
the accused product . . . with the patentee's
commercial embodiment.” …Although in the
recitation of facts, the court in United States
Surgical Corp. v. Hospital Prods. Int'l Pty. Ltd.,
remarked that statements in the Section
510(k) submission “may be construed as
admission of infringement,” the court did not
rely on the submission in the infringement
analysis.”](https://image.slidesharecdn.com/biomedicalstrategyworkshoppresentations-13236109105882-phpapp02-111211074921-phpapp02/85/BioMedical-Strategy-Medical-Devices-Workshop-Presentations-89-320.jpg)
Uploaded byBioMedical Strategy (2004) Ltd.
BioMedical Strategy Medical Devices Workshop Presentations
This FDA warning letter outlines issues with a clinical investigation conducted by Dr. Thomas Beilke between 2008-2009. The FDA inspection found that Dr. Beilke failed to properly conduct or supervise the clinical investigation according to regulations. Specifically, the letter cites that Dr. Beilke did not personally conduct or supervise the investigation as required. The FDA concluded that Dr. Beilke did not adhere to statutory requirements and regulations governing clinical investigations.
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- 1. December 2011 From Idea t Market F Id to M k t Use: P U Practical Notes ti l N t
- 2. From Idea toBedSide: A Practical Guide Orna O PhD O Oz, BioMedical Strategy (2004) Ltd gy ( ) Clinical & Regulatory Affairs Group December 2011
- 3. Medical Product A MultidisciplinaryProject December 2011
- 4. Medical Product Technological Solution Market Medical Need Analysis Regulatory R l t Patentability Scientific Evidence & Reimbursement Funding December 2011
- 5. Main Target Markets g EU USA December 2011
- 6. Main Target Markets g Combined Planning and Workflow December 2011
- 7. Medical Device Definition • 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 December 2011
- 8. Premarket Phase Regulatory Strategy Pre Submission (NB, FDA) Quality Assurance December 2011
- 9. Project Steps ( j p (Life Cycle) y ) • Research & Proof of Concept • Regulatory Strategy (for regulated products) • Project initiation – System/Market Requirements • Specifications and Risk Analysis / Traceability Matrix • R&D framework • Verification and Validation: bench, ex-vivo, in vivo • Clinical • Submission/s market approvals • Market penetration December 2011
- 10. Regulatory Path g y •Proof of Concept •Requirements q •Risk Assessment US EU Regulatory Pathway Finalize discussion with Notified gy and Clinical Strategy body for Strategy Pre- IDE Development + Quality System Q Verification & Validation Poolability Clinical Study (OUS) IDE Clinical Study (US and OUS) IDE CE Mark 510(k) Clearance/PMA Approval December 2011
- 11. Regulatory Strategy • Intended use & Indications for use (Claim) • Regulatory Cl R l Classification ifi i • Applicable standards and guidelines • Proposed pre clinical Testing pre-clinical • 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 • Re-assess business plan – designated product, timelines and budget Alternative approaches
- 12. Claim / IntendedUse Intended U I t d d Use: What is being done g Sometimes where it is being done Sometimes why it is being done Indications: Diseases Patients Subsets December 2011
- 13. 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 December 2011
- 14. CDRH’s Risk BasedParadigm g Class I Class II Class III December 2011
- 15. Classification Determination of Risk Risk / Benefit where Benefit Outweighs Risk December 2011
- 16. Classification Determination of Risk User/Pt g Mitigation Environment Generic type Circumstances Claim December 2011
- 17. Risk-Benefit (Safety / Efficacy) •A great deal of emphasis is placed on the importance of clinical data in demonstrating the safety and effectiveness of a medical device. Still….Non-clinical data also can be critical to understanding device safety and effectiveness. Medical devices often h M di l d i ft have attributes th t cannot b t t d using tt ib t that t be tested i clinical methods alone and that play a major role in the safety or effectiveness of the device. FDA Guidance (Aug 2011): “Factors to Consider when Making Benefit-Risk Determinations in Medical Device Premarket Review” Clinical and non-clinical data play a role in the benefit-risk determination December 2011
- 18. Classification December 2011
- 19. R D Animal Design Ex i E vivo Bench B h & Development Clinical December 2011
- 20. System Requirements • Intended use • Target population (indications) • Product description • Applicable Standards And Guidelines • Requirements (safety, performance, usability, marketing): – Output / Outcome (measures or outcome of treatment), accuracy / efficacy – Biocompatibility, cleanness ( p y, (sterility) y) – Mechanical and electrical properties – Compatibility with target anatomy – C Compatibility with other products ( tibilit ith th d t (accessories, additional i dditi l under the same procedure….) – End user December 2011
- 21.
- 22. Standards and Guidelines To be routinely surveyed December 2011
- 23. Standards and Guidelines •General: – Regulatory decisions and Classification – Design Control – Clinical Cli ical – Biocompatibility – Electrical El t i l – Software •S Specific / Special ifi S i l – Specific to that family of devices or specific properties of device (material, energy type and i fd i ( i l d level, etc.) December 2011
- 24. Traceability Matrix A MatrixBased Approach December 2011
- 25. Traceability Matrix Functional Clinical Clinical Risk Verification & Validation Requirements Risk Mitigation by Type of Evaluation Specific Procedures Biocompatible Systemic Materials and Biocompatibility Compliance with ISO 10993- p adverse design testing; animal 1:2009 Biological evaluation reaction, testing, clinical data of medical devices - Part 1 death (e.g., Cyotoxicity, Sensitization, Etc.)) Electrical and EM Serious Design and Electrical and EM Test Report demonstrating safe burns, IFU Testing compliance with EN 60601-1 death (2006) + A1 & A2 - Medical Electrical Equipment - Part 1: General Requirements for Basic Safety And Essential Performance Compatible with C tibl ith Injury, I j Design d D i and Specific b S ifi bench tests, ht t other equipment In death (e.g., IFU animal testing, the clinical arena pacemaker clinical data will not function) f ti ) Functional Injury, Design and Specific functionality (mechanical/tissue death IFU tests, animal testing, interaction/target clinical data organ)) December 2011
- 26. Risk Analysis • Patient Injury Effect of (expected Failure complications) Harm • Device Deterioration • Design Cause of Failure • Manufacturing • User Error • Design • Protective measures Mitigation g in manufacturing process • Labeling (IFU) December 2011
- 27. Risk Assessment Table (1st approach) A Matrix Based Approach December 2011
- 28. Risk Assessment Table (1st approach) Mode of Effect of Cause of Risk Control Verification Failure / Failure / Harm Failure (Mitigation) Hazard Hazards Related to BIOLOGICAL Hazards Related to MECHANICAL Hazards Related • Loss or 1. Inadequate 1. Design (e.g., Device Functionality Testing to Deterioration of D t i ti f specification ifi ti designed with d i d ith PERFORMANCE Device. 2. Insufficient integrated radiopaque • Patient Injury control of markers) manufacturin 2. Protective measures in g processes manufacturing process: QC inspections during production Hazards Related Patient Injury re-use of single Labeling IFU includes the following warning: to DEVICE USE use device “The System is a single-use device and is intended for single patient use only. Re – using the device is a potential for cross-infection. Do not attempt to clean or re-sterilize the System. Reprocessing the device may damage the device making it unsafe for use. ” December 2011
- 29. Project / ProductMilestones Always use Science & Regulatory Based Tools!! December 2011
- 30. Project / ProductMilestones • Ongoing Development •Quality System Q y y • Design Freeze • Pre clinical V&V •Manufacturing • Premarket Clinical Investigation P k Cli i l I i i • Submission for market clearance/approval • Postmarket activities (clinical study/ies) December 2011
- 31. The V&V Loop p Animal A i l Design Ex vivo Bench & Development Clinical December 2011
- 32. Bench Testing December 2011
- 33. Safety / Performance/ Usability Evaluations • Correlate with Risk Assessment / Traceability Matrix • Plan a matrix of tests where more than one safety and/or efficacy aspect can be evaluated at once, using the same group of devices • Design • Objectives (safety and/or performance and/or usability) and EndPoints (mechanical usability ….) (mechanical, usability, ) • Measures: quantitative, qualitative (scores) • Success criteria • Number of repetitions (confidence/reliability) • Conduct • E Experimental set-up i t l t • Validated set-up (the model, calibrated tools)
- 34. In Vivo AnimalTesting December 2011
- 35. Safety / Performance/ Usability Evaluations • C Correlate with Risk Assessment / Traceability l t ith Ri k A t T bilit Matrix • Design • Objectives (safety and/or performance and/or usability) and EndPoints (biological, mechanical, usability, ..) • Success criteria • Measures: quantitative, qualitative (scores) • Animal model and target anatomy in the animal • Study group/s (& sample size) • Follow up periods (acute, xx–day) • Experimental Procedure • Simulated clinical procedure / relevant aspects and arena • Histology – analysis approach and parameters with a gy y pp p recognized pathologist
- 36. The Animal Lab Conduct (from day 1) • Selection of appropriate animal laboratory (GLP, other accepted certification? No certification) tifi ti ) • Pre-visit to selected laboratory (facility, staff) • Di Discuss with the investigator and staff your ith th i ti t d t ff planned study • Conduct of a controlled and monitored study (Case Report Forms, accountability and traceability of: investigated devices, animals, y g , , explanted parts)
- 37. Clinical Evidence December 2011
- 38. Clinical Strategy gy Post-market Post market . . . Study # 3 Study #2 FIM Investigational/pre-market December 2011
- 39. Clinical Strategy gy Correlated with Risk Assessment / Traceability Matrix December 2011
- 40. The Key toMarket 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 December 2011
- 41. 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 December 2011
- 42. Safety / Performance/ Usability Evaluations E l ti • Design • Define type of study (example: single arm, prospective, open label) • Define Objectives (safety and/or performance and/or usability) and EndPoints (safety/complications, mechanical, usability, efficacy/clinical outcome….) • Determine indicated population (eligibility criteria) • Determine success criteria • Define measures: qualitative (scores), quantitative • Define study group/s ( & sample size) • Define the appropriate follow up periods (acute, xx– follo p (ac te day) • Experimental Procedure = Clinical procedure December 2011
- 43. Safety / Performance/ Usability Evaluations E l ti Clinical Demonstration of Risk / Benefit Design is based on scientific claims, relevant peer li l literature & regulatory l submissions December 2011
- 44. Conduct of Trial December 2011
- 45. 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 December 2011
- 46. IP Site Selection Laws of Country Costs Scientific Publications Location / Market Availability Personnel & Facilities Regulatory Expected subjects eligibility subjects- December 2011
- 47. Investigator Selection g Opinion L d O i i Leader A il bilit Availability December 2011
- 48. Study y Management & Monitoring December 2011
- 49. FDA Warning Letters g Some Examples December 2011
- 50. FDA Warning Letter(1) Between July 26 and August 24, 2010, Thomas R. Beilke, representing the U.S. Food and Drug Administration (FDA), conducted an investigation of your former practice practice. During the course of the inspection, Mr. Beilke met with you to review your conduct of a clinical investigation (Protocol (b)(4), titled "(b)(4)") performed for (b)(4). You were the investigator for this clinical investigation between March 2008 and March 2009…….. From our review of the establishment inspection report and the documents submitted with th t report, we conclude th t th d t b itt d ith that t l d that you did not adhere to the applicable statutory requirements and FDA regulations governing the conduct of clinical investigations. 1. You failed to ensure that the investigation was conducted according to the signed investigator statement, in that you failed to g g g , y personally conduct or supervise the clinical investigation [21 CFR 312.60]. 2. You failed to ensure that the investigation was conducted acco di g to the investigational plan [21 CFR 312 60] according i estigatio al la 312.60]. December 2011
- 51. FDA Warning Letter(2) This Warning Letter is to inform you of objectionable conditions observed during the Food and Drug Administration (FDA) inspection conducted at Orthocon, Inc. Orthocon Inc ... The purpose of this inspection was to determine whether activities as sponsor of the clinical studies (b)(4) and (b)(4) complied with applicable federal regulations. This letter also requests prompt corrective action to address the violation cited and discusses your written response dated September 23 2010 to the 23, noted violation. Failure to secure the investigator’s compliance. [21 CFR 812.46(a)]: Sponsors are responsible for monitoring and ensuring compliance of clinical investigators participating in the investigation. A sponsor who discovers that an investigator is not complying with the signed agreement the investigational plan applicable FDA regulations or agreement, plan, regulations, any conditions of approval imposed by the reviewing IRB or FDA shall promptly either secure compliance or discontinue shipments of the device to the investigator and terminate the investigator’s participation in the investigation. December 2011
- 52. FDA Warning Letter(3) During an inspection of your firm located in Or-Akivaon June 20, 2011, through June 23, 2011, an i investigator f i from the United S h i d States Food and Drug d d Administration (FDA) determined that your firm manufactures the XX and the YY. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body…… Specifically, the XX and the YY were cleared under Kxxxxxx and Kxxxxxx, respectively. Our inspection revealed that your firm modified the devices by (b)(4) to the XX and the YY (b)(4). A new 510(k) is required for this modification as it represents a significant change to the design of the devices…… As A a result, FDA may t k steps t refuse th lt take t to f these products, k d t known as "detention without physical examination," until these violations are corrected. December 2011
- 53. In Summary Clinical & Regulatory Affairs is about implementing cost effective strategies and i l ti g t ff ti t t gi d tools for a valuable project It is the umbrella, from early development through market approval and up to p pp p post-marketing activities g (market penetration), to support the Company in the bringing to the markets a reasonably safe and effective product It is the right means to create value and minimize (mitigate) liability in a least burdensome way December 2011
- 54. Standards G idli St d d & Guidelines Some Useful Links December 2011
- 55. Global and EU •Link for European directive and Guidance documents (MEDDEV) http://www.meddev.info/ http://www meddev info/ • Link for standards of all directives (medical and non medical) in Europe http://ec.europa.eu/enterprise/policies/european- h // / i / li i / standards/documents/harmonised-standards-legislation/list-references/ December 2011
- 56. Global and EU(Cont.) ( ) • Link for standards non active implantable medical devices in Europe http://ec.europa.eu/enterprise/policies/european http://ec europa eu/enterprise/policies/european- standards/documents/harmonised-standards-legislation/list- references/medical-devices/index_en.htm • Link for standards active implantable medical devices in Europe http://ec.europa.eu/enterprise/policies/european- standards/documents/harmonised-standards-legislation/list- t d d /d t /h i d t d d l i l ti /li t references/implantable-medical-devices/index_en.htm • GHTF http://www.ghtf.org December 2011
- 57. FDA • FDA basicsfor Industry http://www.fda.gov/ForIndustry/FDABasicsforIndustry/default.htm http://www fda gov/ForIndustry/FDABasicsforIndustry/default htm • FDA general: http://www.fda.gov/default.htm h // fd /d f l h • Medical Devices: http://www.fda.gov/MedicalDevices/default.htm • Combination products: http://www.fda.gov/CombinationProducts/default.htm • Device Advise http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/defa ult.htm December 2011
- 58. FDA (Cont.) • Searchfor FDA Guidance Documents (by office/ year/keyword): http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Guid http://www fda gov/MedicalDevices/DeviceRegulationandGuidance/Guid anceDocuments/default.htm • Link to FDA databases (510(k) PMA Adverse Events Classifications (510(k), PMA, Events, Classifications, Registration and Listing, Standards, TPLC, 21CFR, etc) http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm • CDRH Organization structure and directors (personnel) p g http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm 127854.htm • CDRH post approval studies database: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma_pas.cfm December 2011
- 59. 2010 - 2011Interesting FDA Guidance • D f Guidance f I d Draft G id for Industry and F d and D d Food d Drug Administration S ff - Ad i i i Staff Investigational Device Exemptions (IDE) for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies • Draft Guidance for Industry and Food and Drug Administration Staff - Applying Human Factors and Usability Engineering to Optimize Medical Device Design • Draft Guidance for Industry and FDA Staff: FDA a d Industry Procedures a t Gu da ce o dust y a d Sta : and dust y ocedu es for Section 513(g) Requests for Information under the Federal Food, Drug, and Cosmetic Act34 • Guidance for Industry and FDA Staff: General Considerations for Animal Studies for Cardiovascular Devices3 December 2011
- 60. 2010 - 2011Interesting FDA Guidance (Cont.) • Draft Guidance for Industry, Clinical Investigators, Institutional Review Boards, and Food and Drug Administration Staff - FDA Decisions for Investigational Device Exemption (IDE) Clinical Investigations • Draft Guidance for Industry and Food and Drug Administration Staff - De Novo Classification Process (Evaluation of Automatic Class III ovo C ass cat o ocess ( va uat o o uto at c C ass Designation)2 • Oversight of Clinical Investigations — A Risk Based Approach to Risk-Based Monitoring • D f Guidance f I d Draft G id for Industry and F d and D d Food d Drug Administration S ff - Ad i i i Staff Factors to Consider when Making Benefit-Risk Determinations in Medical Device Premarket Review December 2011
- 61. Useful Links 2010 - 2011 Interesting FDA Guidance • Draft Guidance for Industry, Clinical Investigators, and Food and Drug y, g , g Administration Staff - Design Considerations for Pivotal Clinical Investigations for Medical Devices • Guidance for Industry and FDA Staff - 510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device • Draft Guidance for Industry and FDA Staff - Commercially Distributed In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only: Frequently Asked Questions December 2011
- 62. Useful Links 2010 - 2011 Interesting FDA Guidance (Cont ) (Cont.) • Guidance for Industry and FDA Staff: In Vitro Diagnostic (IVD) Device Studies - Frequently Asked Questions • Draft Guidance for Industry, Third Parties and FDA Staff: Medical Device ISO 13485:2003 Voluntary Audit Report Submission Program December 2011
- 63. The Innovation Paradigm: Good or Bad? Maier Fenster Copyright 2011 All rights reserved No Portion may be Copied or Otherwise Reproduced without Express Written Permission
- 64. Disclaimer • The purposeof this presentation is to communicate concepts. There is no guarantee that the information presented is complete or up-to-date. • Also, information is not legal advice. Legal advice is when you apply information to a situation. • Go to a lawyer for legal advice. • Go to a patent attorney for patent-related advice. • Go to a regulatory expert for regulatory advice.
- 65. Why are wehaving this talk • We all live innovation, but sometimes it seems like too much of a good thing • Try to illustrate the tensions between innovation and success, with special emphasis on regulatory affairs and clinical trials • Will attempt to give tools to model, not always solve, the problems • An experimental talk
- 66. Outline • What is the innovation paradigm • What is the ideal regulatory process • What is the ideal development process • What is the reality & why • A suggested attitude • Some practical examples • Q&A and discussion
- 67. The Innovation Paradigm •Premise: We will succeed because our product is better • Assumption: Our product is better because we have secret discovery/better engineers/better understanding/blind luck • Conclusion: we need to show that our product is better • Corollary: we hire people and work hard to make our product better • Emphasis: not “better”; “MUCH better”
- 68. Ideal regulatory process#1 • Plan new product based on existing market/product • Develop new product • Show equivalence of new product & old product • Ta-da • Insight: more innovation requires more proof • And: small improvement requires more proof
- 69. Ideal regulatory process#2 • Have great new idea • Develop great new device • Run clinical trials • Succeed • Ta-da • Insight: all’s well that ends well
- 70. Ideal development process #1 • Have idea • Create design, taking into account ideal manufacturing method and usage method • Build device • Have it work first time • Ta-da • Insight: we all like risk-free R&D
- 71. Ideal development process #2 • Have idea • Build prototype • Test prototype - fast • Redesign device based on test results & user input • Repeat until great product is created • Ta-da • Insight: moving fast with lots of money is good
- 72. Reality knocks -basics • Only the lucky ones have innovation which does not affect functioning • New product can be better in: – Manufacturability – Shelf life – Ease of use – Reliability in body – Function – Side effects/Safety – Other
- 73. Reality knocks -basics, cont. • New device might (only) be different, not better • When will we find out that device is better? • Will the market change? • Will competition change the game? • Experimental failure is bad
- 74. Reality knocks -process • What are chances experiments will work as advised? • How long must we wait for that (e.g., avoid adverse results)? • Will there be NO inputs from users? data analysis? • What if a problem is discovered? • What if device is not good enough? • What if a better device is possible?
- 75. Reality knocks -people • People involved believe in innovation • People involved want to cure patients • Researchers are NOT mere technicians • Hype, advisors & investors • Engineers do not just change gears • Building the company brand • Pressure from agile development processes
- 76. Reality knocks -IP • There is a war going on – enemy is watching • One must think several steps ahead • What you tell one government agency, others will know about • Several court cases on point • Device development cycle is slower than IP cycle • IP can drive development by publishing ideas • IP & device specs do not fully overlap • When is innovation understood? And if it changes? • Make IP match the selection for regulatory approval • Problems and opportunities
- 77. What is yourreality? • Be aware of conflicting forces that encourage, discourage and/or channel innovation and discussion of innovation. Who is involved for each “party”? • How do you balance need for showing innovation with need for showing lack of innovation. • How is innovation channeled? • Money. Business. Working product. How are they linked to innovation and its consequences? • Are all “risks” from experiments taken into account?
- 78. Some suggested activities •Micro-level – Collaboration between IP and regulatory advisors, and also with publishing bodies, such as researchers – re-consider (everything) based on changes in target, on a regular basis • Divert innovation activities to: – clear “stage II” products/features – less regulated issues • Play the country game • Prepare alternative pathways – File IP based on prediction of results – Develop and advance designs based on IP problems • Experiment also for IP - Early
- 79. Case study –unneeded battle • Story of a client who was not careful • They wanted to get a patent – so they explained innovation • They wanted 510(k) so they explained how innovation was same as prior art • Then they got threatened, with other side basing its belief on the 510(k) • Good news: they came to us • We did lots of stuff, including a new 510(k) filing • We won. But (Sun Tzu): – The greatest victory, is the battle not fought.
- 80. Case study -hindsight • What FDA wants to get comfort on is not exact opposite of what patent office wants to see for inventive step – USPTO does not care much about safety. FDA does – FDA is happy if device works same as old device due to lack of insight in the past into operation mechanism and its consequences; USPTO would be happy too • Somebody could have made an educated decision • Somebody could have coordinated between the “professionals” • One should be aware of case law
- 81. More hindsight • Talkingabout your own previous and current devices is bad enough • Talking about the competition is worse • Any statements can be used against you in a court of law • Courts (& management) tend to confuse patent and product. Don’t help them get confused • Risk: (partial) admission of infringement • Risk: admission of fraud • Risk: attracting litigation
- 82. Case study –loose lips sink ships • Client wanted 510(k). Presented device as substantially equivalent. • Client wanted investor hype. Published paper showing innovation • FDA was not happy. • Hindsight – if you generate hype, make sure it does not reflect on your regulatory processes. • Nice if hype does reflect on your IP processes.
- 83. Principles of Law-I •In determining infringement it is settled law that the accused device should be compared to the patent claims and not to a particular product manufactured by the patent holder. • Nevertheless, this idea is sometimes confusing to patent holders and also to courts, which find it easier to compare the accused device to a concrete device than to compare it to abstract claims. • Furthermore, such admissions can be used an opening to claim willfulness or fraud on the patent office.
- 84. Principles of Law-II •Even if the admission is not considered a complete admission of infringement, the wording of the 510(k) could still help the patentee by positively mentioning some of the features of the claims as being the same in both devices.
- 85. Principles of Law-III •In Pall Corp. v. Hemasure Inc., the Federal Circuit used the disclosure in the 510(k) as a guide to determine whether there was infringement. However, there apparently was no utilization of the patentee’s device as a predicate.
- 86. Principles of Law-IV •In Electro Scientific Industries Inc. v. Dynamic Details Inc., the Federal Circuit discussed whether the information in the FDA 510(k), which was not supplied to the USPTO, could be considered fraud on the patent office, in that the submission contained drawings made by a sub- contractor. Based on the facts of the case it decided that this did not raise an inventorship issue.
- 87. Principles of Law-V •In United States Surgical Corp. v. Hospital Products International PTY Ltd., the US District Court for Connecticut made the following statement: • “The defendants have gone so far as to cause statements to be made that may be construed as admissions of infringement. For example, on October 28, 1980, HPI submitted to the United States Food and Drug Administration a §510(k) pre-market notification, signed by Blackman, of its intention to sell its 30, 55, and 90 medium and large series of DLUs, as well as its GA/ANAST (an earlier name for the defendants’ ILA DLU). It was stated in the notification that these devices were equivalent to their USSC counterparts.” • However, the court did not utilize this admission in finding infringement.
- 88. Principles of Law-VI •In a footnote in Clintec Nutrition Co. v. Baxa Corp., the US District Court for the Northern District of Illinois states: • “Clintec also relies on Baxa's Section 510(k) submission to the Food and Drug Administration (“FDA”), representing that Baxa's and Clintec's compounders are “substantially equivalent.” Clintec does not, however, point me to an affirmative representation in the submission that Baxa's compounders “sort.” … Baxa gained the Agency's approval to market its compounders without undergoing a more extensive approval process, because Baxa was able to demonstrate that its compounders were “substantially equivalent” to Clintec's. “
- 89. Principles of Law-VII •“A device is ‘substantially equivalent’ if it has the same intended use and the same technological characteristics as those of the existing device. • “Thus, the 510(k) submission compares the accused product, Baxa's compounders, with the commercial embodiment of the ‘010 patent, Clintec's compounders. “ [I]t is error for a court to compare in its infringement analysis the accused product . . . with the patentee's commercial embodiment.” …Although in the recitation of facts, the court in United States Surgical Corp. v. Hospital Prods. Int'l Pty. Ltd., remarked that statements in the Section 510(k) submission “may be construed as admission of infringement,” the court did not rely on the submission in the infringement analysis.”
- 90. Principles of Law-VIII •It seems clear that a court will consider statements made in a 510(k) as being statements against interest. The extent of the damage will depend of course on the statements made and how they impact on the issues before the court. • Thus, it is important to weigh carefully all statements made in a 501(k). This is not limited to comparisons with predicate devices but also includes statements regarding the operation of the device, etc.
- 91. Summary • Innovation isgood, but at some point it needs to be controlled and/or channeled • IP and regulatory processes interact. Strongly. And both are affected by experiments. • Use a good regulatory advisor • Like lots of life – timing, expectation matching and risk management • Not all bad – one can get synergy by matching business, IP and regulatory
- 92. A Harmonized andSynchronized Pathway for Reimbursement and Regulation December 1st, 2011 Amir Inbar, CEO Mediclever Ltd. © Copyright 2012 Mediclever Ltd. All rights reserved. Proprietary and confidential. Neither this presentation nor any information it contains may be viewed, disclosed, published, reproduced or used for any 1 / 51 purpose without prior written approval from Mediclever.
- 93. One Slide Resume 1. Established Mediclever in 2006 2 / 51
- 94. Agenda 1. What 2. When 1. What (is ‘Reimbursement’) 3. How 4. Where 2. When (Should We Start Dealing With It) 3. How (Do We Take Care of It) 4. Where (In Which Countries First) 3 / 51
- 95. What is ‘Reimbursement’? 1.What 2. When 1. What (is ‘Reimbursement’) 3. How 4. Where 2. When (Should We Start Dealing With It) 3. How (Do We Take Care of It) 4. Where (In Which Countries First) 4 / 51
- 96. What is ‘Reimbursement’? Relax… 1. What 2. When 3. How 4. Where 5 / 51
- 97. What is ‘Reimbursement’? Stakeholders 1. What 2. When 3. How 4. Where Stakeholders 6 / 51
- 98. What is ‘Reimbursement’? Stakeholders 1. What 2. When Healthcare Providers: Patients: 3. How Hospital 4. Where ASC / Imaging Center Physician Payers: Government Insurance Companies / Sickness Funds / Primary Care Trusts 7 / 51
- 99. What is ‘Reimbursement’? Financing a Healthcare System 1. What 2. When 3. How 4. Where Financing a Healthcare System 8 / 51
- 100. What is ‘Reimbursement’? Financing a Healthcare System 1. What 2. When Public / Statutory: 3. How Sources (Citizens): Collection (Payers): 4. Where Taxes from the general population Social health insurance from: • Employers: • Employees 9 / 51
- 101. What is ‘Reimbursement’? Financing a Healthcare System Sources Collection Paid To For 1. What (Citizens): (Payers): (Providers): (Patients): 2. When 3. How 4. Where Public / Statutory Out of Pocket Reimbursement Private / Complementary 10 / 51
- 102. What is ‘Reimbursement’? Reimbursement Workflow 1. What 2. When 3. How 4. Where Reimbursement Workflow 11 / 51
- 103. What is ‘Reimbursement’? Reimbursement Workflow 1. What 1. The healthcare provider uses CODES 2. When to tell the Payer: 3. How a. The problem Diagnostic Code/s 4. Where b. The service Procedure Code/s c. Add. details Age, Sex, etc. 2. The Payer checks if the above combination has COVERAGE 3. If positive, the Payer reimburses the healthcare provider according to the applicable PAYMENT schedule 12 / 51
- 104. What is ‘Reimbursement’? Reimbursement Workflow 1. What For each setting: There are different: 2. When 3. How Inpatient CODES, 4. Where Procedures COVERAGE Outpatient guidelines, and Procedures PAYMENT levels Office based Procedures 13 / 51
- 105. What is ‘Reimbursement’? 1.What 2. When Meaning of Life 3. How “While I can explain the 4. Where meaning of life, I don’t dare try to explain how the reimbursement system works” 14 / 51
- 106. Agenda 1. What 2. When 1. What (is ‘Reimbursement’) 3. How 4. Where 2. When (Should We Start Dealing With It) 3. How (Do We Take Care of It) 4. Where (In Which Countries First) 15 / 51
- 107. When Should WeStart Dealing With It? Past 1. What Past 2. When Healthcare costs Containable 3. How 4. Where Following FDA/CE Reimbursement is ‘given’ Decision Makers for a Healthcare Providers market launch Reimbursement Not important strategy Planning for Just prior to launch reimbursement 16 / 51
- 108. When Should WeStart Dealing With It? Past 1. What 2. When 3. How 4. Where 17 / 51
- 109. When Should WeStart Dealing With It? Present 1. What 2. When 3. How So, what has changed? 4. Where 18 / 51
- 110. When Should WeStart Dealing With It? Present 1. What Past Present 2. When Healthcare costs Containable Soaring 3. How 4. Where Following FDA/CE Reimbursement is Reimbursement only if ‘given’ there’s clinical + economic value Decision Makers for a Healthcare Providers Healthcare Providers + market launch Payers Reimbursement Not important Required by Investors, strategy inc. resources and timelines Planning for Just prior to launch At an early stage reimbursement 19 / 51
- 111. When Should WeStart Dealing With It? Past 1. What Errors Solutions 2. When • Product features prevent utilization of • Consider reimbursement implications 3. How existing reimbursement mechanisms during product design 4. Where • Targeted applications / indications / • Consider reimbursement implications settings / populations - delay when defining your market / reimbursement marketing strategy • FDA/CE application prevents • Consider reimbursement reimbursement implications before applying for FDA clearance or CE mark • Clinical trials not leveraged to also • Add reimbursement parameters to generate reimbursement evidence your planned clinical trials • Price not optimized when launching • You know what to do… product or negotiating with a potential 20 / 51 investor/buyer
- 112. Agenda 1. What 2. When 1. What (is ‘Reimbursement’) 3. How 4. Where 2. When (Should We Start Dealing With It) 3. How (Do We Take Care of It) 4. Where (In Which Countries First) 21 / 51
- 113. How Do WeTake Care of It? 1. What 1. Reimbursement Main Decision 4. Evidence Planning 9. Implementation Landscape Report Makers • Value story • User base, stakeholders’ support 2. When • Codes, coverage • Economic model & payment Healthcare • Issue a Billing Guide, utilize existing Providers • Points for clinical • Reimbursement reimbursement mechanisms 3. How study protocol strategy • Stakeholders’ 4. Where Payers feedback • Apply for new reimbursement mechanisms 2. Regulatory Class I (NS/M) •Technical file Landscape 8. Preparation / Application Report Class I (S/M) 3. Quality EU Manag. •Regulatory Class IIa System status Class IIb •Design •Device Control 5. Clinical 6.Perform 7.Quality classification Class III procedures Study Clinical Manag. •Design dossier •Intended use Protocol Study System •Other QS & indications •Review / •Clin. Eval. •FDA QSR / Class III aspects for •PMA for use write report ISO 13845 US/EU pre- •Regulatory Class II study •510(k) route compliance Class I US 22 / 51
- 114. How Do WeTake Care of It? 1. What 1. Reimbursement Gather data Landscape Report – Determine relevant For each setting: There are different: 2. When • Codes, coverage & payment settings. Inpatient CODES 3. How • Reimbursement Procedures strategy Outpatient COVERAGE 4. Where guidelines Procedures PAYMENT levels Office based Procedures – Check for relevant 1. The healthcare provider uses CODES codes, coverage policies to tell the Payer: and payment rates. a. Problem Diagnostic Code/s b. Service Procedure Code/s c. Details Age, Sex, etc. 2. The Payer checks if the above combination has COVERAGE 3. If positive, the Payer reimburses the healthcare provider according to the applicable PAYMENT 23 / 51 schedule
- 115. How Do WeTake Care of It? 1. What 2. When 3. How 4. Where 24 / 51
- 116. How Do WeTake Care of It? 1. What 1. Reimbursement Gather data Landscape Report – Determine relevant For each setting: There are different: 2. When • Codes, coverage & payment settings. Inpatient CODES 3. How • Reimbursement Procedures strategy Outpatient COVERAGE 4. Where guidelines Procedures PAYMENT levels Office based Procedures – Check for relevant 1. The healthcare provider uses CODES codes, coverage policies to tell the Payer: and payment rates. a. Problem Diagnostic Code/s b. Service Procedure Code/s c. Details Age, Sex, etc. 2. The Payer checks if the above combination – Statistics has COVERAGE 3. If positive, the Payer reimburses the healthcare provider according to the applicable PAYMENT 25 / 51 schedule
- 117. How Do WeTake Care of It? 1. What 1. Reimbursement Main Decision This enables us to: Landscape Report Makers 2. When • Codes, coverage •Define the most relevant Decision Makers for the & payment Healthcare Providers reimbursement of you’re the product. 3. How • Reimbursement strategy •Formulate an initial reimbursement strategy for the 4. Where Payers new product in the selected markets (Europe, US). 26 / 51
- 118. How Do WeTake Care of It? 1. What 1. Reimbursement Main Decision In parallel, a Regulatory Landscape Report determines the Landscape Report Makers product’s classification, intended use, indications for use 2. When • Codes, coverage & payment Healthcare and the anticipated regulatory route. Providers 3. How • Reimbursement strategy 4. Where Payers Regulatory 2. Regulatory Class I (NS/M) Landscape Report Class I (S/M) Reimbursement EU •Regulatory Class IIa status Class IIb •Device classification Class III •Intended use & indications Intended use Affects possible reimbursement for use Class III •Regulatory Class II route Substantially equivalent = substantially equivalent Class I US payment 27 / 51
- 119. How Do WeTake Care of It? 1. What 1. Reimbursement Main Decision At the next stage, when the company prepares for its Landscape Report Makers clinical study (if needed), it typically: 2. When • Codes, coverage & payment Healthcare Providers •Implements the relevant parts of its Quality Management 3. How • Reimbursement strategy System (e.g., Design Controls and other QS aspects 4. Where Payers essential for US and EU pre-study compliance). •Starts writing its clinical study protocol. 2. Regulatory Class I (NS/M) Landscape Report Class I (S/M) 3. Quality EU Manag. •Regulatory Class IIa System status Class IIb •Design •Device Control 5. Clinical classification Class III procedures Study •Intended use Protocol •Other QS & indications •Review / Class III aspects for for use write US/EU pre- •Regulatory Class II study route compliance Class I US 28 / 51
- 120. How Do WeTake Care of It? Long before the clinical study begins, we 1. What 1. Reimbursement Main Decision 4. Evidence Planning Landscape Report Makers plan the required ‘evidence’ for the • Value story 2. When • Codes, coverage • Economic model product’s reimbursement : & payment Healthcare Providers • Points for clinical 3. How • Reimbursement study protocol • Value Story: Claim for clinical AND strategy • Stakeholders’ economic benefits compared to current 4. Where Payers feedback alternatives. • Economic Model: Quantify the economic benefit, allow for sensitivity analysis and use as a sales tool. 2. Regulatory Class I (NS/M) Landscape • Reimbursement Related Parameters: Report Class I (S/M) 3. Quality Manag. Integrate in the study protocol. EU •Regulatory Class IIa System status • Stakeholders’ Feedback: Verify support Class IIb •Design •Device Control 5. Clinical of the relevant Decision Makers, if the classification Class III procedures Study claims in the Value Story are proven •Intended use Protocol according to the presented clinical study •Other QS & indications •Review / Class III aspects for protocol. for use write US/EU pre- •Regulatory Class II study route compliance Class I US 29 / 51
- 121. How Do WeTake Care of It? 1. What 2. When Regulatory Approval ≠ Reimbursement 3. How 4. Where Regulatory entities Reimbursement entities (FDA, NBs, …) (CMS, Sickness Funds, …) Does the product: do what it claims? improve outcomes? Is the product: safe & effective? reasonable & necessary? Data from: controlled settings real world Support of: KOLs medical society/ies Cost: not relevant may be key 30 / 51
- 122. How Do WeTake Care of It? 1. What 1. Reimbursement Main Decision 4. Evidence Planning Now, the clinical trial may be Landscape Report Makers conducted and the resulting • Value story 2. When • Codes, coverage • Economic model ‘evidence’, substantiating the claims & payment Healthcare • Reimbursement Providers • Points for clinical in the Value Story, should be 3. How study protocol strategy published. • Stakeholders’ 4. Where Payers feedback 2. Regulatory Class I (NS/M) Landscape Report Class I (S/M) 3. Quality EU Manag. •Regulatory Class IIa System status Class IIb •Design •Device Control 5. Clinical 6.Perform classification Class III procedures Study Clinical •Intended use Protocol Study •Other QS & indications •Review / •Clin. Eval. Class III aspects for for use write report US/EU pre- •Regulatory Class II study route compliance Class I US 31 / 51
- 123. How Do WeTake Care of It? Seed Funding Round A 1. What 1. Reimbursement Main Decision 4. Evidence Planning Landscape Report Makers Raise funding: • Value story 2. When • Codes, coverage • Economic model • At this stage, in order to finance & payment Healthcare • Reimbursement Providers • Points for clinical their clinical trial, many companies 3. How study protocol strategy raise their growth funding round • Stakeholders’ 4. Where feedback (also referred as Series A round). Payers 2. Regulatory Class I (NS/M) Landscape Report Class I (S/M) 3. Quality EU Manag. •Regulatory Class IIa System status Class IIb •Design •Device Control 5. Clinical 6.Perform classification Class III procedures Study Clinical •Intended use Protocol Study •Other QS & indications •Review / •Clin. Eval. Class III aspects for for use write report US/EU pre- •Regulatory Class II study route compliance Class I US 32 / 51
- 124. How Do WeTake Care of It? 1. What 1. Reimbursement Main Decision 4. Evidence Planning Completion of QMS Landscape Report Makers • Value story 2. When • Codes, coverage • Economic model If the company has not already done & payment Healthcare Providers • Points for clinical so, the quality management system 3. How • Reimbursement study protocol strategy can be completed to ensure it • Stakeholders’ 4. Where feedback complies with US and/or European Payers requirements. 2. Regulatory Class I (NS/M) Landscape Report Class I (S/M) 3. Quality EU Manag. •Regulatory Class IIa System status Class IIb •Design •Device Control 5. Clinical 6.Perform 7.Quality classification Class III procedures Study Clinical Manag. •Intended use Protocol Study System •Other QS & indications •Review / •Clin. Eval. •FDA QSR / Class III aspects for for use write report ISO 13845 US/EU pre- •Regulatory Class II study route compliance Class I US 33 / 51
- 125. How Do WeTake Care of It? 1. What 1. Reimbursement Main Decision 4. Evidence Planning • Europe: Submit the Technical File Landscape Report Makers or the Design Dossier • Value story 2. When • Codes, coverage • Economic model & payment Healthcare • USA: apply for FDA Clearance (510 Providers • Points for clinical 3. How • Reimbursement study protocol (k)) or Approval (PMA). strategy • Stakeholders’ 4. Where Payers feedback 2. Regulatory Class I (NS/M) •Technical file Landscape 8. Preparation / Application Report Class I (S/M) 3. Quality EU Manag. •Regulatory Class IIa System status Class IIb •Design •Device Control 5. Clinical 6.Perform 7.Quality classification Class III procedures Study Clinical Manag. •Design dossier •Intended use Protocol Study System •Other QS & indications •Review / •Clin. Eval. •FDA QSR / Class III aspects for •PMA for use write report ISO 13845 US/EU pre- •Regulatory Class II study •510(k) route compliance Class I US 34 / 51
- 126. How Do WeTake Care of It? 1. What 1. Reimbursement Main Decision 4. Evidence Planning 9. Implementation Landscape Report Makers • Value story • User base, stakeholders’ support 2. When • Codes, coverage • Economic model & payment Healthcare • Issue a Billing Guide, utilize existing Providers • Points for clinical • Reimbursement reimbursement mechanisms 3. How study protocol strategy • Stakeholders’ 4. Where Payers feedback • Apply for new reimbursement mechanisms In case existing reimbursement mechanisms •Technical file (Codes, Coverage, Payment) exist, we will 8. Preparation / Application • Develop a dossier to convince Healthcare Providers to purchase your new product. 5. Clinical 6.Perform 7.Quality Study Clinical Manag. •Design dossier Protocol Study System Otherwise: •Review / •Clin. Eval. •FDA QSR / •PMA write report ISO 13845 • After verifying a sufficient user-base and •510(k) support from the medical community, we will apply for new codes, coverage policies and favorable payment rates. 35 / 51
- 127. How Do WeTake Care of It? 1. What 2. When 3. How 4. Where 36 / 51
- 128. Agenda 1. What 2. When 1. What (is ‘Reimbursement’) 3. How 4. Where 2. When (Should We Start Dealing With It) 3. How (Do We Take Care of It) 4. Where (In Which Countries First) 37 / 51
- 129. Where (In WhichCountries First)? 1. What 2. When 1. Potential market 3. How 2. Supportive environment: 4. Where IP protection Regulatory process Reimbursement 38 / 51
- 130. Where (In WhichCountries First)? Potential Market 1. What 2. When 1. Potential market 3. How 2. Supportive environment: 4. Where IP protection Regulatory process Reimbursement 39 / 51
- 131. Where (In WhichCountries First)? Potential Market 1. What 3 Types of Healthcare Systems 2. When 3. How Private Payer and Provider are separated entities Payers 4. Where Clearer definition of covered procedures. Detailed reimbursement lists. Statutory Sickness Funds There must be an accurate procedure code (with its coverage and payment rate). Payer and Provider are not so separated No need for a clear definition of coverage. NHS Reimbursement also relies on ‘block contracts’, ‘balance Grants’, etc. 40 / 51
- 132. Where (In WhichCountries First)? Potential Market 1. What Healthcare Expenditure per Capita ($US PPP) 2. When 3. How Private 7,538 4. Where Payers Statutory 3,737 Sickness Funds 3,696 3,129 NHS 2,870 2,902 41 / 51 $US Source: OECD Indicators 2008 (http://stats.oecd.org)
- 133. Where (In WhichCountries First)? Potential Market 1. What Healthcare Expenditure per Capita (% of GDP) 2. When 3. How Private 16.0% 4. Where Payers Statutory 10.5% Sickness Funds 11.2% 8.7% NHS 9.1% 9.0% 42 / 51 $US Source: OECD Indicators 2008 (http://stats.oecd.org)
- 134. Where (In WhichCountries First)? Potential Market 1. What Healthcare Expenditure Sources 2. When 3. How Private (47) (12) (41) 4. Where Payers Statutory (77) (10) (13) Sickness Funds (78) (15) (7) % Public / Statutory (83) (11) % Private / Complementary NHS (77) (20) % Out of Pocket (73) (21) 43 / 51 $US Source: OECD Indicators 2008 (http://stats.oecd.org)
- 135. Where (In WhichCountries First)? Potential Market 1. What Spending on medical technology: €187B 2. When 3. How • US: 42% Medical technology is defined as wheelchairs, pacemakers, orthopedic 4. Where • Germany (DM): 11% shoes, spectacles and contact lenses, • Japan (JP): 10% insulin pens, hip prostheses, condoms, • France: (FR): 05% oxygen masks, dental floss, MRI scanners, pregnancy tests, surgical • UK: 04% instruments, bandages, syringes, life- • China (CH): 02% support machines, etc. CH UK FR JP DM US 0 10 20 30 40 50 60 70 80 90 100 44 / 51 Source: Eucomed Medical Technology Brief, May 2007
- 136. Where (In WhichCountries First)? Potential Market 1. What Medical Technologies Funding (% of GDP) 2. When 3. How Private 0.71% 4. Where Payers Statutory 0.92% Sickness Funds 0.62% 0.36% NHS 0.5% 0.46% 45 / 51 $US Source: AdvaMed, UK Medical Technology Issues, CEO Toolkit, January 2005
- 137. Where (In WhichCountries First)? Supportive Environment 1. What 2. When 1. Potential market 3. How 2. Supportive environment: 4. Where IP protection Regulatory process Reimbursement 46 / 51
- 138. Where (In WhichCountries First)? Supportive Environment – IP Protection IP protection : 1. What 9 – Best 7 2. When 0 – Worst 6 Germany 3. How France USA 4. Where Japan 5 UK China Israel 4 IP India Brazil 3 2 1 Software piracy rate 80% 60% 40% 20% 0% 47 / 51 PWC Innovation Scorecard
- 139. Where (In WhichCountries First)? Supportive Environment – Regulatory Ease of regulatory 1. What approval: 9 9 – Easiest Israel 2. When 0 – Most difficult 8 3. How 7 India France 4. Where 6 UK Germany 5 Regulatory USA 4 Brazil 3 China Japan 2 1 Regulatory approval time, months 30 24 18 12 6 months months months months months 48 / 51 PWC Innovation Scorecard
- 140. Where (In WhichCountries First)? Supportive Environment - Reimbursement 1. What 2. When 3. How 4. Where Reimbursement 49 / 51 PWC Innovation Scorecard
- 141. Where (In WhichCountries First)? Supportive Environment 1. What 2. When 3. How 4. Where IP Regulatory Reimbursement 50 / 51 PWC Innovation Scorecard
- 142. The End 1. What 2.When Thank You For Listening 3. How 4. Where Amir Inbar, CEO http://www.mediclever.com amir@mediclever.com http://twitter.com/mediclever 050.837.1711 http://mediclever.com/blog UK Office: Israel Office: • 27 Old Gloucester St., • 6 Te’ena St., • London WC1N 3AX • Modiin 71799 • uk@mediclever.com • il@mediclever.com 51 / 51 • +44.208.099.7435 • +972.50.837.1711
- 143. A Notified Bodyperspective when revising and judging the conformity of a device for granting CE marking Hester Hasper
- 144. Contents Introductionto DEKRA: bigger picture & business line medical DEKRA’s expertise & market access Conformity assessment by the notified body & the D&D process New applications (dossier): what are we looking at? Review of the approach to obtain CE Changes / revisions / extension: what is the approach followed?
- 145. Bigger picture: BusinessLine Medical within DEKRA DEKRA GROUP (HQ Stuttgart, Germany) DEKRA Operating in 29 European countries as well as in North America, Brazil, 21 000 South Africa and China. Organized in 4 Business Units comprising a total of 180 consolidated companies. DEKRA Industrial 5 000 Generating 1.7 billion euros in sales and employs 21000 staff. Testing & DEKRA Testing and Certification is Certification 1000 part of the Business Unit DEKRA Industrial with 5000 business and Medical technical professionals.
- 146. Business Line Medical Characteristics Competence areas ● Involves testing and certification of medical ● Audits devices, and auditing of medical device companies ● Product assessments ● Certification ● A leading top 5 global Notified Body in Medical device certification ● Product testing (IEC 60601) ● Training ● Recognized market leader in high risk devices ● Strong positions in Netherlands, Germany & USA CE0124 & CE0344 ● Recognized body by EU, the FDA, Health Canada ● Test labs in Arnhem, Stuttgart & Dresden.
- 147. Business Line MedicalGlobal Network One global team of experts, Arnhem CE0124 Paris no country organizations, Stuttgart CE0344 no barriers San Francisco Philadelphia Tokyo תל אביב
- 148. Expertise and Knowledgeat DEKRA Cardiovascular Products with surgery animal tissue Minimal invasive High-tech start-up surgery companies Ophthalmic Intravascular surgery catheters Wound care Intra ocular lenses products Soft tissue implants Body contouring implants Active Implantable devices Active Medical devices High tech start-up companies Emerging technologies High risk products
- 149. Market Access EUmarket access – Notified Body USA for: • FDA third party review 510(k) • AIMDD 90/385/EEC program • MDD 93/42/EC • FDA trial audits Taiwan • IVDD 98/79/EC • Recognition formally only for EU, • Animal tissue directive Swiss companies are also eligible 2003/32/EC for the Taiwanese TCP program • Blood directive 2000/70/EC Australia ⇒ For all directives full scope • Recognition (formally only for EU) Services – Quality system Japan certification to: • Working on accreditation under • ISO 9001 the Japanese Pharmaceutical Affairs law • ISO 13485 China • ISO 14001 (environmental) • no role for Third Party Canada • Consulting organization in Beijing • CMDCAS ISO 13485 that assists medical device manufacturers with approvals for China (SFDA, CQC)
- 150. clinical Pre-clinical Bench testing From idea to market use design requirements IDEA
- 151. From idea tomarket use … evidence gathering: Build up the evidence for safety & performance certificate IDEA Bench testing requirements Pre-clinical design clinical audit audit Performance In a perfect world: Biological safety All studies + Packaging integrity completed, Stability documented dossier dossier in DHF Sterilization validation Etc.
- 152. Project risks duringproduct development … Dossier review for the device: questions … certificate IDEA Bench testing requirements Pre-clinical design clinical audit audit Number of patients in clinical study? + Support of shelf life claim? dossier dossier Transportation testing of packaging? Material selection vs biocompatibilty? Why is it considered a medical device?
- 153. Evaluation of thedossier by the NB: What? Product description and claims • Why is the product a medical device? • What is the intended use? • Mode of action? • Presence of drug substance, animal tissue, human blood derivative Classification Risk management for the design, use and manufacturing of the product Performance testing (design verification, including animal tests) Safety testing • electrical safety • mechanical safety • biological safety • software Packaging integrity Stability / shelf life STED Guidance Sterilization validation (GHTF) Clinical evaluation
- 154. Evaluation of thedossier by the NB: How? Selection of the reviewer (qualifications): field of expertise Build dossier Review of the documentation • Use of harmonized standards (EN ISO) • Use of guidance documents (MEDDEVs, NB MED, GHTF) Dossier DHF • State of the art techniques IN Consultation for the review • Experts for FEA, sterilization, software, biocompatibility etc. Review DEKRA • Clinical experts in the field (physicians) • For drug device combinations: competent authorities • For devices with human blood derivative: EMA Review CM Peer review within DEKRA Combine with audit results OUT Recommendation to certification management CE certificate CE mark
- 155. Project risks duringproduct development … When to approach your notified body? IDEA Bench testing requirements Pre-clinical design clinical Is the proposed plan to obtain evidence Your Your for safety and performance acceptable? plan to plan to • biological safety evaluation obtain obtain • Sterilization validation evidence evidence • Bench tests …… • Size and approach for clinical study
- 156. Project risks duringproduct development … When to approach your notified body? certificate IDEA Bench testing requirements Pre-clinical design clinical audit audit Your - Answers to the specific questions + Your Review Review plan to plan to DEKRA report … - Expectations resulting report … dossier dossier obtain obtain review from the review evidence evidence ……
- 157. Evaluation of theplan by the Notified Body Over-all approach for CE: Regulatory Pathway Review RPR • Is the approach acceptable? Specific questions • Packaging evaluation acceptable? Write plan • Software validation approach? • Testing of biological safety? IN Clinical evaluation: Clinical Pathway Review: CPR Review DEKRA EXAMPLES EXAMPLES Q: Is it possible to leverage part x, y, z for safety testing from device A Q: Is it acceptable to perform a Review CM to B? limited study with x patients to show safety of the device? A: This can be accepted provided that similarity is shown … provided A: This can be accepted OUT that … Q: Is accelerated aging acceptable 1. EXPECTATIONS to show the device has 18 m shelf Q: We want to limit clinical 2. CONCLUSION life? evaluation to animal test and literature review, is that
- 158. Evaluation of changesby the NB: what? The new product shall meet the essential requirements of the MDD certificate When a change is filed: Δ? SOP SOP • What has changed? • What is de gap between CE marked product and IFU / / IFU new product? labels Manufacturing labels Δ? methods • What are the risks associated? • How are these Δ? Δ? materials risks mitigated? Δ? Size IFU / / IFU labels labels packaging Claims, intended use
- 159. Evaluation of changesby the NB: how? Selection of the reviewer (qualifications): field of expertise Gap analysis complete? Comparable - Similar - Identical Review of the documentation Consultation for the review • Experts for FEA, sterilization, software, biocompatibility etc. • Clinical experts in the field (physicians) • For drug device combinations: competent authorities • For devices with human blood derivative: EMA Peer review within DEKRA Additional audit needed? Recommendation to certification management Notification of approval and/or updated CE certificate
- 160. Summary DEKRA Certification:Top 5 notified body – your guide for safeguarding quality in medical products and processes. Design dossier review and audit of QMS are the basis for CE marking • Review of the dossier – use of standards, structure pref. STED • Control of risks for surprises in the end by assessment of the overall plan and/or clinical protocol • Review of changes – focus on gaps between current & new