ce marking , fda approval and associated regulations for wellness
TRANSCRIPT
www.wellnesshealthinnovation.orgICS Confidential
CE Marking, FDA Approval and Regulations for Wellness
11 January 2011
CE Marking , FDA Approval and
Associated Regulations for Wellness
Overview
• Managing the Device Regulatory Approval Process for Multiple Countries
• An Overview of Key Elements of EU/US and Worldwide Regulatory Strategies and How to Align them with other Business Strategies
Questions you may have!!
• Is my product a Medical Device? • If so, what is its classification? • How do I show it complies with the Essential
Requirements? • How do I construct a Technical File? • What must I do to meet the risk management
requirements? • Does compliance with international/national
standards help? • How do I prepare a clinical evaluation report?
Questions you may have!!
• Do I need a Notified Body? • If so, how do I select one? • Do I need a certified quality management
system? • Does my device labelling meet the requirements? • What do I need to do if I assemble procedure
packs? • What should be included on my Declaration of
Conformity? • What are my post-market reporting obligations?
Similarities/Differences Global Regulatory Approaches
5
Regulatory Body
Class (Risk Based)
MarketApproval
Quality System
Adverse Event Reporting
United States (U.S.) FDA Center for Devices and Radiological Health
Class 1, 2, 3 ExemptClearanceApproval letter
QS Regulations 21 CFR 820
MDR
Canada Health Canada
Class I, II, III, IV
MD License except Class I
CAN/CSA ISO 13485
Vigilance System
EU (European Union)
Competent AuthorityNotified Body
Class I, IIa, IIb, III
CE Marking MDD/IVDDEN ISO 13485
Vigilance System
Japan Ministry of Health, Labour and Welfare
Class 1, 2, 3, 4
MHLW Approval certificate
QMS Ordinance ISO 13485
Vigilance System
Australia Therapeutic Goods Administration
Similar to EU. Similar to EU ISO 13485 Vigilance System
Go to
Background Information
• Regulatory Applications for Devices– United States
• 510(k) – Substantial Equivalence w/ Predicate(s)– Intended Use / Indications for Use– Similar Technology– Assumed Safety and Effectiveness
• PMA – Proves Safety and Effectiveness– No Predicate– Requires Animal and Human Trials
• DeNovo – Risk Based Classification– 510(k) – NSE + DeNovo Application– Requires Special Controls Guidance Document
• Others– 513(g) – Request for Classification– RFD – Request for Designation (combination products)– IDE – Investigational Device Exemption
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Background Information– Europe
• CE Marking– Product Approval
» MDD Compliance (Essential Requirements)» Technical File / Technical Dossier
– QMS Approval» ISO 13485» Notified Body Audit
– Canada• License Application• QMS Certification
– ISO 13485:2003– Canadian Registrar– Additional CMDCAS Requirements
– Others• Nearly all 1st and 2nd World Countries have requirements for marketing medical
devices
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US vs. the E.U. and Canada• Similarities
– Risk Based Device Categorization Schemas• US – Class I to Class III• EU – Class I, Class IIa, Class IIb, Class III• Canada – Class I to Class IV
– Premarket Clearance / Approval Required• Amount / Type of Data Submitted is Based on Risk• Clinical Data Required for High Risk Devices
– Quality Management System Required• cGMP and ISO 13485:2003 are very similar• Post Market Monitoring and Adverse Event Filing Required• Audits are performed to verify compliance
– Clinical Trials Required Pre-Approval• US – IRB + IDE for Significant Risk, IRB only for Non-Significant Risk• EU – Ethics Board + Competent Authority for non-CE devices, Ethics Board only for CE devices• Canada – Ethics Board + ITA for Class II – Class IV devices, Ethics Board only for Class I
devicesCONFIDENTIAL
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US vs. the E.U. and Canada• Differences
– Risk Based Device Categorization Schemas
• Canada and EU use “Rules Based” approach, not lists of devices and associated classifications (pro-codes)
• Dramatic Differences in resulting Device Classifications (i.e. – US Class III could be EU Class I)
– Premarket Clearance / Approval Required
• Canada and EU have a single, scalable application type vs. US with two distinct dissimilar applications (tech file vs. 510(k) and PMA)
• Canadian Review done by Governmental Agency• EU Review done by Third Party (Notified Body) or Self Declaration• US Review done by both FDA and Third Parties
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US vs. the E.U. and Canada• Differences
– Quality Management System Required
• cGMP and ISO 13485:2003 are very similar• Post Market Monitoring and Adverse Event Filing Required• Audits are performed to verify compliance
– Clinical Trials
• EU - All Devices Required Clinical Data Report (Annex X)– Allows a combination of Literature Review, Clinical Information, and Clinical
Data– Class IIb and Class III require Clinical Data
• Canada – Class III and Class IV typically require clinical data• US – Class III PMA Devices require Clinical Data. Some 510(k) devices require
clinical data to support Substantial Equivalence.
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Key Differences
• What Differences Are Most Important
– Classification – Determines Application and Clinical Data Requirements
– Quality Management System Timing Requirements• QMS must be IMPLEMENTED and AUDITED to obtain CE• Only selected cGMP elements must be implemented to submit 510(k)• PMA products require Pre-Approval cGMP audit
– ISO / CMDR Assessments vs. cGMP Audits• ISO – Audits performed by Notified Body you select and pay• CMDR – Audits performed by Canadian Registrar you select and pay• cGMP – Performed by Regulatory Authority• Canada / EU – Supportive approach assuming compliance• FDA – Punitive approach assuming non-complianceCONFIDENTIAL
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Other Things To Remember• US
– Not all Class I Devices are exempt from any or all of the following:
• Design Controls– Specific Class I device require application of Design Controls
• cGMP– Even cGMP exempt have to comply with Complaint and Records
Requirements• 510(k)
• EU– EU Device Classification to determine Routes to Market (Annex combinations from
MDD)
• Nearly always more than 1 route• ISO 13485 is not called out by MDD• It is possible to need FULL 13485 compliance for other countries but not for EU.
Sales / Marketing plan is important to a good strategy
With so many regulations out there…… where do you start?
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Regulatory Strategy Overview
• What Is A Regulatory Strategy?
– A Path for Regulatory Clearance / Approval in a Market– Understanding of the Requirements to Obtain Clearance or Approval
• Application Type• Requirements for Bench Testing• Requirements for Animal Testing• Requirements for Human Testing• Quality Management System Requirements• Quality Management System Certifications
– Understanding the Sequence of Events and Timing– Understanding the Integration of Business and Regulatory Activities– Understanding of Expected Regulatory / QMS Costs
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Regulatory Strategy Overview• Why Is It Important?
– Cost• Nearly always more than one available strategy• Wide variation in cost based on application type
– 510(k) - $20K to $2M– PMA - $500K – $10M
– Time-To-Market• 510(k) – Prep Time + 90 day review (real world 180 days)• PMA – Prep Time + 180 day review (real world 2+ years)
– Raising Capital• Regulatory Strategy now required for many types of financing• Due diligence often includes Regulatory Strategy review
– Organizational Structure and Hiring• What QA / RA resources will be necessary to achieve strategy
– Legal Ramifications of Non-Compliance• Warning Letters, Consent Decrees, Cessation Orders, Import Bans, etc.
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Regulatory Strategy Overview• How Do I Know If My Current Strategy Is Good Enough?
– Your Strategy Should Answer All Of The Following:• Where will the product be distributed in the first 36 months after launch?• What Regulatory Applications will be required in each country?• Which applications require clinical or animal data?• If Clinical Data is required, where will trials be conducted and what applications /
approvals are required for the clinical trial?• How long is the average review time for my application type and product type in
each country?• Are there fees associated with the Regulatory Application?• For each application, what is the likelihood of approval / clearance and what are
the risk areas?• Do any of the applications require corresponding QMS inspections / certifications
(pre-approval inspection, ISO certification, etc.)?• Do Design Controls apply to my product and if so, how will I meet these
requirements?• Where the finished product will be manufactured
Common Mistakes / Misconceptions
• General– No Written Regulatory Strategy– Failure to Follow Design Controls / Start Design Controls Too Late– Regulatory Requirements are Black and White
• United States– My product will be cleared through a 510(k)– Clinical and Animal Trials are required for all US Applications– There is no middle ground between 510(k) and PMA– The 510(k) process today is the same as 1 year ago
• Internationally– CE is Easy– If I get a 510(k) or PMA, I can ship my product anywhere in the world– Clinical Trials can be conducted without rules outside the US
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Outsourced design and mfgOutsourced design and mfg
• If the design or manufacturing of a device is done by a third party, you must demonstrate that you have adequate controls in place to ensure the continued efficient operation of their quality system.
© 2005 Emergo Group, Inc. Australia > Canada > The Netherlands > United States 1.800.956.6588
SoftwareSoftware
• Will now be considered an active medical device, whether integral with the device or as a standalone product.
• Software validation will also be an Essential Requirement.
© 2005 Emergo Group, Inc. Australia > Canada > The Netherlands > United States 1.800.956.6588
EU Device Regulations - WEEE
• Labeling Requirement – Wheelie Bin • Disposal Instruction Requirements• EN 50419
© 2005 Emergo Group, Inc. Australia > Canada > The Netherlands > United States 1.800.956.6588
Consider Regulatory Issues Early On
• It is easily understood that new companies developing innovative technologies to solve clinical problems concentrate their thoughts on optimizing the technology for the intended use, and keeping the company afloat financially.
• Unfortunately, unless issues relating to regulatory compliance are also considered early on, this can lead to problems closer to the time when the product is ready for marketing.
• This may result in delays, sometime substantial, in having the product available for sale, with knock‐on effects in meeting critical investment milestones, and even to the survival of the company itself.
• The company's initial business plan should include an outline regulatory strategy that is closely aligned to the marketing strategy (indeed, the regulatory strategy may often drive the marketing strategy).
Reminders to take home.....• When planning to expand your empire, investigate what is required
for each country and budget as appropriate.
• Understand the process– Do Not Make Assumptions
• Choose the correct partner/distributor– You don’t want to repeat the process, Take the time to choose
wisely.
• Plan your Timelines– Give yourself plenty of time
• Country Approval is not CHEAP
Medical Device Myth’s• “My marketing strategy will drive my regulatory strategy.”
• “I’m just a one‐person start‐up – I don’t need Regulatory support yet.”
• “I’ve made a prototype, so now I can give it to a clinician to try it out.”
• “I’ve read the regulations. I don’t need to do all that, do I?”
• CEO/MD or Board of Directors
“I don’t need to understand about QA/RA. I’ve got a QA/RA manager to do that.”
• Making the wrong strategic decisions early on, based on bad regulatory understanding or advice, can lead companies into "blind alleys," hindering their ability to meet investor milestones and raise additional funds.
www.wellnesshealthinnovation.orgICS Confidential
CE Marking, FDA Approval and Regulations for Wellness
11 January 2011