BioMedical Strategy Medical Devices Workshop Presentations

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December 1st, 2011 - BioMedical Strategy Medical Devices Workshop -Speakers Presentations

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BioMedical Strategy Medical Devices Workshop Presentations

  1. 1. December 2011 From Idea t Market F Id to M k t Use: P U Practical Notes ti l N t
  2. 2. From Idea to BedSide: A Practical Guide Orna O PhD O Oz, BioMedical Strategy (2004) Ltd gy ( ) Clinical & Regulatory Affairs Group December 2011
  3. 3. Medical ProductA Multidisciplinary Project December 2011
  4. 4. Medical Product Technological Solution MarketMedical Need Analysis Regulatory R l tPatentability Scientific Evidence & Reimbursement Funding December 2011
  5. 5. Main Target Markets gEU USA December 2011
  6. 6. Main Target Markets gCombined Planning and Workflow December 2011
  7. 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. 8. Premarket PhaseRegulatory Strategy Pre Submission (NB, FDA) Quality Assurance December 2011
  9. 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. 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 StrategyPre-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. 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. 12. Claim / Intended UseIntended UI t d d Use: What is being done g Sometimes where it is being done Sometimes why it is being doneIndications: Diseases Patients Subsets December 2011
  13. 13. Implications of Claim SPECIFICITY LEVEL1. Identification of function Tool Claim2. Identification of tissue type an organ system or (higher clinical Identification of a specific evidence)) organ3. Identification of a particular disease or target population4. Identification of an effect on clinical outcome Clinical Claim December 2011
  14. 14. CDRH’s Risk Based Paradigm gClass I Class II Class III December 2011
  15. 15. ClassificationDetermination of Risk Risk / Benefit whereBenefit Outweighs Risk December 2011
  16. 16. Classification Determination of Risk User/Pt g MitigationEnvironment Generic type Circumstances Claim December 2011
  17. 17. Risk-Benefit (Safety / Efficacy)•A great deal of emphasis is placed on the importance ofclinical data in demonstrating the safety and effectivenessof a medical device.Still….Non-clinical data also can be critical tounderstanding device safety and effectiveness.Medical devices often hM di l d i ft have attributes th t cannot b t t d using tt ib t that t be tested iclinical methods alone and that play a major role in the safety oreffectiveness of the device.FDA Guidance (Aug 2011): “Factors to Consider when Making Benefit-RiskDeterminations in Medical Device Premarket Review” Clinical and non-clinical data play a role in the benefit-risk determination December 2011
  18. 18. Classification December 2011
  19. 19. R D Animal DesignEx iE vivo Bench B h & Development Clinical December 2011
  20. 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. 21. December 2011
  22. 22. Standards and Guidelines To be routinely surveyed December 2011
  23. 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. 24. Traceability MatrixA Matrix Based Approach December 2011
  25. 25. Traceability MatrixFunctional Clinical Clinical Risk Verification & ValidationRequirements Risk Mitigation by Type of Evaluation Specific ProceduresBiocompatible 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 demonstratingsafe burns, IFU Testing compliance with EN 60601-1 death (2006) + A1 & A2 - Medical Electrical Equipment - Part 1: General Requirements for Basic Safety And Essential PerformanceCompatible withC tibl ith Injury, I j Design d D i and Specific b S ifi bench tests, ht tother 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 dataorgan)) December 2011
  26. 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. 27. Risk Assessment Table (1st approach)A Matrix Based Approach December 2011
  28. 28. Risk Assessment Table (1st approach) Mode of Effect of Cause of Risk Control Verification Failure / Failure / Harm Failure (Mitigation) HazardHazards Relatedto BIOLOGICALHazards RelatedtoMECHANICALHazards Related • Loss or 1. Inadequate 1. Design (e.g., Device Functionality Testingto Deterioration of D t i ti f specification ifi ti designed with d i d ithPERFORMANCE Device. 2. Insufficient integrated radiopaque • Patient Injury control of markers) manufacturin 2. Protective measures in g processes manufacturing process: QC inspections during productionHazards 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. 29. Project / Product Milestones Always use Science & Regulatory Based Tools!! December 2011
  30. 30. Project / Product Milestones• 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. 31. The V&V Loop p Animal A i l DesignEx vivo Bench & Development Clinical December 2011
  32. 32. Bench Testing December 2011
  33. 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. 34. In Vivo Animal Testing December 2011
  35. 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. 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. 37. Clinical Evidence December 2011
  38. 38. Clinical Strategy gy Post-market Post market. . .Study # 3Study #2 FIM Investigational/pre-market December 2011
  39. 39. Clinical Strategy gy Correlated with RiskAssessment / Traceability Matrix December 2011
  40. 40. The Key to Market Penetration yA breakthrough technology is great but does notensureens re market s ccess successRegulatory approvals are meaningful milestones •In creating value for strategic agreements and funding •In entrance to the marketClinical evidence (data) is the leading forceto successful market penetration andpositioning December 2011
  41. 41. Clinical Strategy MEDDEV 2 7 1 2.7.1 Stage 1* Stage 2Identify clinical data from Appraisal of individual data sets • Suitability• Literature searching &/or• Clinical experience &/or • Contribution of performance• Clinical investigation and safetyGenerate 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. 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. 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. 44. Conduct of Trial December 2011
  45. 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. 46. IP Site Selection Laws of CountryCosts Scientific PublicationsLocation /Market AvailabilityPersonnel &Facilities Regulatory Expected subjects eligibility subjects- December 2011
  47. 47. Investigator Selection g Opinion L d O i i Leader A il bilit Availability December 2011
  48. 48. Study yManagement & Monitoring December 2011
  49. 49. FDA Warning Letters g Some Examples December 2011
  50. 50. FDA Warning Letter (1)Between July 26 and August 24, 2010, Thomas R. Beilke, representing theU.S. Food and Drug Administration (FDA), conducted an investigation of yourformer practice practice.During the course of the inspection, Mr. Beilke met with you toreview your conduct of a clinical investigation (Protocol (b)(4), titled"(b)(4)") performed for (b)(4). You were the investigator for this clinicalinvestigation between March 2008 and March 2009……..From our review of the establishment inspection report andthe documents submitted with th t report, we conclude th tth d t b itt d ith that t l d thatyou did not adhere to the applicable statutory requirementsand FDA regulations governing the conduct of clinicalinvestigations.1. You failed to ensure that the investigation was conductedaccording to the signed investigator statement, in that you failed to g g g , ypersonally conduct or supervise the clinical investigation [21 CFR312.60].2. You failed to ensure that the investigation was conductedacco di g to the investigational plan [21 CFR 312 60]according i estigatio al la 312.60]. December 2011
  51. 51. FDA Warning Letter (2)This Warning Letter is to inform you of objectionable conditions observedduring the Food and Drug Administration (FDA) inspection conducted atOrthocon, Inc.Orthocon Inc ...The purpose of this inspection was to determine whether activities assponsor of the clinical studies (b)(4) and (b)(4) complied withapplicable federal regulations.This letter also requests prompt corrective action to address the violationcited and discusses your written response dated September 23 2010 to the 23,noted violation. Failure to secure the investigator’s compliance. [21CFR 812.46(a)]: Sponsors are responsible for monitoring andensuring compliance of clinical investigators participating in theinvestigation.A sponsor who discovers that an investigator is not complying with thesigned agreement the investigational plan applicable FDA regulations or agreement, plan, regulations,any conditions of approval imposed by the reviewing IRB or FDA shallpromptly either secure compliance or discontinue shipments of the deviceto the investigator and terminate the investigator’s participation in theinvestigation. December 2011
  52. 52. FDA Warning Letter (3)During an inspection of your firm located in Or-Akivaon June 20, 2011, throughJune 23, 2011, an i investigator f i from the United S h i d States Food and Drug d dAdministration (FDA) determined that your firm manufactures the XX and theYY. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (theAct), 21 U.S.C. § 321(h), these products are devices because they are intendedfor 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 orfunction of the body……Specifically, the XX and the YY were cleared under Kxxxxxx and Kxxxxxx,respectively. Our inspection revealed that your firm modified thedevices by (b)(4) to the XX and the YY (b)(4). A new 510(k) is requiredfor this modification as it represents a significant change to the designof the devices……AsA 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 arecorrected. December 2011
  53. 53. In Summary Clinical & Regulatory Affairs is aboutimplementing cost effective strategies andi l ti g t ff ti t t gi d tools for a valuable projectIt is the umbrella, from early development throughmarket approval and up to p pp p post-marketing activities g(market penetration), to support the Company in thebringing to the markets a reasonably safe and effectiveproduct It is the right means to create value and minimize (mitigate) liability in a least burdensome way December 2011
  54. 54. Standards G id liSt d d & Guidelines Some Useful Links December 2011
  55. 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. 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. 57. FDA• FDA basics for 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. 58. FDA (Cont.)• Search for 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. 59. 2010 - 2011 Interesting 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. 60. 2010 - 2011 Interesting 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. 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. 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. 63. The Innovation Paradigm: Good or Bad? Maier Fenster Copyright 2011 All rights reservedNo Portion may be Copied or Otherwise Reproduced without Express Written Permission
  64. 64. Disclaimer• The purpose of 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. 65. Why are we having 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 77. What is your reality?• 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. 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. 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. 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. 81. More hindsight• Talking about 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. 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. 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. 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. 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. 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. 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. 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 Baxas Section 510(k) submission to the Food and Drug Administration (“FDA”), representing that Baxas and Clintecs compounders are “substantially equivalent.” Clintec does not, however, point me to an affirmative representation in the submission that Baxas compounders “sort.” … Baxa gained the Agencys 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 Clintecs. “
  89. 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, Baxas compounders, with the commercial embodiment of the ‘010 patent, Clintecs compounders. “ [I]t is error for a court to compare in its infringement analysis the accused product . . . with the patentees commercial embodiment.” …Although in the recitation of facts, the court in United States Surgical Corp. v. Hospital Prods. Intl 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. 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. 91. Summary• Innovation is good, 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. 92. A Harmonized and Synchronized Pathway for Reimbursement and RegulationDecember 1st, 2011Amir Inbar, CEOMediclever Ltd.© Copyright 2012 Mediclever Ltd. All rights reserved. Proprietary andconfidential. Neither this presentation nor any information it containsmay be viewed, disclosed, published, reproduced or used for any 1 / 51purpose without prior written approval from Mediclever.
  93. 93. One Slide Resume 1. Established Mediclever in 20062 / 51
  94. 94. Agenda1. What2. When 1. What (is ‘Reimbursement’)3. How4. 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. 95. What is ‘Reimbursement’?1. What2. When 1. What (is ‘Reimbursement’)3. How4. 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. 96. What is ‘Reimbursement’? Relax…1. What2. When3. How4. Where 5 / 51
  97. 97. What is ‘Reimbursement’? Stakeholders1. What2. When3. How4. Where Stakeholders 6 / 51
  98. 98. What is ‘Reimbursement’? Stakeholders1. What2. When Healthcare Providers: Patients:3. How Hospital4. Where ASC / Imaging Center Physician Payers: Government Insurance Companies / Sickness Funds / Primary Care Trusts 7 / 51
  99. 99. What is ‘Reimbursement’? Financing a Healthcare System1. What2. When3. How4. Where Financing a Healthcare System 8 / 51
  100. 100. What is ‘Reimbursement’? Financing a Healthcare System1. What2. 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. 101. What is ‘Reimbursement’? Financing a Healthcare System Sources Collection Paid To For1. What (Citizens): (Payers): (Providers): (Patients):2. When3. How4. Where Public / Statutory Out of Pocket Reimbursement Private / Complementary 10 / 51
  102. 102. What is ‘Reimbursement’? Reimbursement Workflow1. What2. When3. How4. Where Reimbursement Workflow 11 / 51
  103. 103. What is ‘Reimbursement’? Reimbursement Workflow1. What 1. The healthcare provider uses CODES2. When to tell the Payer:3. How a. The problem Diagnostic Code/s4. 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. 104. What is ‘Reimbursement’? Reimbursement Workflow1. What For each setting: There are different:2. When3. How Inpatient CODES,4. Where Procedures COVERAGE Outpatient guidelines, and Procedures PAYMENT levels Office based Procedures 13 / 51
  105. 105. What is ‘Reimbursement’?1. What2. When Meaning of Life3. How “While I can explain the4. Where meaning of life, I don’t dare try to explain how the reimbursement system works” 14 / 51
  106. 106. Agenda1. What2. When 1. What (is ‘Reimbursement’)3. How4. 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. 107. When Should We Start Dealing With It? Past1. What Past2. When Healthcare costs Containable3. How4. 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. 108. When Should We Start Dealing With It? Past1. What2. When3. How4. Where 17 / 51
  109. 109. When Should We Start Dealing With It? Present1. What2. When3. How So, what has changed?4. Where 18 / 51
  110. 110. When Should We Start Dealing With It? Present1. What Past Present2. When Healthcare costs Containable Soaring3. How4. 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. 111. When Should We Start Dealing With It? Past1. What Errors Solutions2. When • Product features prevent utilization of • Consider reimbursement implications3. How existing reimbursement mechanisms during product design4. 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. 112. Agenda1. What2. When 1. What (is ‘Reimbursement’)3. How4. 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. 113. How Do We Take Care of It?1. What 1. Reimbursement Main Decision 4. Evidence Planning 9. Implementation Landscape Report Makers • Value story • User base, stakeholders’ support2. When • Codes, coverage • Economic model & payment Healthcare • Issue a Billing Guide, utilize existing Providers • Points for clinical • Reimbursement reimbursement mechanisms3. 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. 114. How Do We Take 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 CODES3. How • Reimbursement Procedures strategy Outpatient COVERAGE4. 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. 115. How Do We Take Care of It?1. What2. When3. How4. Where 24 / 51
  116. 116. How Do We Take 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 CODES3. How • Reimbursement Procedures strategy Outpatient COVERAGE4. 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. 117. How Do We Take Care of It?1. What 1. Reimbursement Main Decision This enables us to: Landscape Report Makers2. 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 the4. Where Payers new product in the selected markets (Europe, US). 26 / 51
  118. 118. How Do We Take 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 use2. When • Codes, coverage & payment Healthcare and the anticipated regulatory route. Providers3. How • Reimbursement strategy4. 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. 119. How Do We Take 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 Management3. How • Reimbursement strategy System (e.g., Design Controls and other QS aspects4. 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. 120. How Do We Take Care of It? Long before the clinical study begins, we1. What 1. Reimbursement Main Decision 4. Evidence Planning Landscape Report Makers plan the required ‘evidence’ for the • Value story2. When • Codes, coverage • Economic model product’s reimbursement : & payment Healthcare Providers • Points for clinical3. How • Reimbursement study protocol • Value Story: Claim for clinical AND strategy • Stakeholders’ economic benefits compared to current4. 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. 121. How Do We Take Care of It?1. What2. When Regulatory Approval ≠ Reimbursement3. How4. 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. 122. How Do We Take 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 story2. When • Codes, coverage • Economic model ‘evidence’, substantiating the claims & payment Healthcare • Reimbursement Providers • Points for clinical in the Value Story, should be3. 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. 123. How Do We Take Care of It? Seed Funding Round A1. What 1. Reimbursement Main Decision 4. Evidence Planning Landscape Report Makers Raise funding: • Value story2. When • Codes, coverage • Economic model • At this stage, in order to finance & payment Healthcare • Reimbursement Providers • Points for clinical their clinical trial, many companies3. 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. 124. How Do We Take Care of It?1. What 1. Reimbursement Main Decision 4. Evidence Planning Completion of QMS Landscape Report Makers • Value story2. When • Codes, coverage • Economic model If the company has not already done & payment Healthcare Providers • Points for clinical so, the quality management system3. 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. 125. How Do We Take 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 story2. When • Codes, coverage • Economic model & payment Healthcare • USA: apply for FDA Clearance (510 Providers • Points for clinical3. 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. 126. How Do We Take Care of It?1. What 1. Reimbursement Main Decision 4. Evidence Planning 9. Implementation Landscape Report Makers • Value story • User base, stakeholders’ support2. When • Codes, coverage • Economic model & payment Healthcare • Issue a Billing Guide, utilize existing Providers • Points for clinical • Reimbursement reimbursement mechanisms3. 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. 127. How Do We Take Care of It?1. What2. When3. How4. Where 36 / 51
  128. 128. Agenda1. What2. When 1. What (is ‘Reimbursement’)3. How4. 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. 129. Where (In Which Countries First)?1. What2. When 1. Potential market3. How 2. Supportive environment:4. Where IP protection Regulatory process Reimbursement 38 / 51
  130. 130. Where (In Which Countries First)? Potential Market1. What2. When 1. Potential market3. How 2. Supportive environment:4. Where IP protection Regulatory process Reimbursement 39 / 51
  131. 131. Where (In Which Countries First)? Potential Market1. What 3 Types of Healthcare Systems2. When3. How Private Payer and Provider are separated entities Payers4. 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. 132. Where (In Which Countries First)? Potential Market1. What Healthcare Expenditure per Capita ($US PPP)2. When3. How Private 7,5384. 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. 133. Where (In Which Countries First)? Potential Market1. What Healthcare Expenditure per Capita (% of GDP)2. When3. 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. 134. Where (In Which Countries First)? Potential Market1. What Healthcare Expenditure Sources2. When3. 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. 135. Where (In Which Countries First)? Potential Market1. What Spending on medical technology: €187B2. When3. How • US: 42% Medical technology is defined as wheelchairs, pacemakers, orthopedic4. 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. 136. Where (In Which Countries First)? Potential Market1. What Medical Technologies Funding (% of GDP)2. When3. 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. 137. Where (In Which Countries First)? Supportive Environment1. What2. When 1. Potential market3. How 2. Supportive environment:4. Where IP protection Regulatory process Reimbursement 46 / 51
  138. 138. Where (In Which Countries First)? Supportive Environment – IP Protection IP protection :1. What 9 – Best 72. When 0 – Worst 6 Germany3. How France USA4. 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. 139. Where (In Which Countries First)? Supportive Environment – Regulatory Ease of regulatory1. What approval: 9 9 – Easiest Israel2. When 0 – Most difficult 83. How 7 India France4. 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. 140. Where (In Which Countries First)? Supportive Environment - Reimbursement1. What2. When3. How4. Where Reimbursement 49 / 51 PWC Innovation Scorecard
  141. 141. Where (In Which Countries First)? Supportive Environment1. What2. When3. How4. Where IP Regulatory Reimbursement 50 / 51 PWC Innovation Scorecard
  142. 142. The End1. What2. When Thank You For Listening3. How4. 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. 143. A Notified Body perspective whenrevising and judging the conformity of adevice for granting CE marking Hester Hasper
  144. 144. Contents Introduction to 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?

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