AMI MQP Market & Regulatory Analysis. Kyle Cayabyab Jameel Galloway Matt Hammond Meagan Ward

Transcription

1 AMI MQP Market & Regulatory Analysis Kyle Cayabyab Jameel Galloway Matt Hammond Meagan Ward

2 Overview

3 Percentage PERCENT ARRHYTHMIA CASES THAT ARE AF Percent Arrhythmia Cases that are AF From the graph shown, the majority of arrhythmia cases are Atrial Fibrillation. The Data for Great Britain, France, Germany, and Ireland were found to be inconclusive. However, there is data on the EU in general.

4 PERCENT AF CASES PER CAPITA 2 Percent AF Cases per Capita With about a thousandth or more of each countries citizens suffering from Atrial Fibrillation, a treatment such as ablation would help treat a large amount of people

5 ABLATION PER EP PER YEAR Ablation per EP per Year Based on the data in this graph, India and Australia do not have a sufficient amount of electro physiologists ablating to keep up with the high volume of patients. By introducing an easier method of conducting ablations, the number of EPs ablating could increase.

6 Terms and Acronyms ISO International Organization for Standardization Regulatory/Distributer Liaison Required in most countries when you register a device that originated elsewhere, may act on your behalf in the regulatory process. Notified Body A third party approved by the European Commission, assess conformity to the directive critical for CE marking. Competent Authority A national registrar responsible for the review and tentative approval of CE Marked devices for sale in that nation. STED Summary Technical Document, a harmonized regulatory submission format used by the US, Canada, EU, Australia, and Japan.

7 Characteristics of an Ideal Regulatory Process Usage of third parties in the safety inspection and clinical testing processes (i.e. notified bodies, KFDA appointed inspectors, etc.) Designed regulatory process to an existing gold standard, usually based on the EU, US, or Japanese regulatory processes. Do not mandate their own clinical trials. Streamlined forms and applications, ideally using the STED format.

8 What is a CE Mark? CE Marking indicates compliance with EU directives of safety. Designed to be the gold standard in safety and efficiency. EFTA member states regulatory standards must comply with the CE directive. CE compliant data considered the most universally accepted when registering a medical device both inside and outside the EU.

9 European Market Key Figures Population: 503,500,000 Population over 50: 165,651,500 # Reported Afib Cases: 2,500,000 Ablating EPs: 899 Afib Ablations performed last year: 43,156 Countries within the EFTA represent one of the largest populations and the oldest population, making it the biggest ideal market. Instances of Arrhythmia have nearly doubled in the past five years.

10 CE Marking Process Classify device, appoint EC-REP, contact a Notified Body Implement ISO 13485, Prepare Design Dossier Notified Body issues CE Certificate, prepare Declaration of Conformity Register device at the national level Design Dossier must include clinical data that passes the EU safety test standards Translate packaging and labeling Conduct post-market surveillance, yearly Notified Body audits

11 EU Regulatory Analysis Notified body system is designed to streamline the regulatory process and promote equal access to new technologies across EFTA. Safety is truly enforced by the competent authorities on the national level, making the initial location and standards of clinical trials highly important. Key Figures Time to approval: 3 years Size of Pivotal Trial: patients Estimated Cost: $800,000 - $2,000,000 CE Certificate CE Mark clinical data is the most widely accepted data on the international level. The CE Mark represents access to the single largest possible market, with the shortest and most cost efficient means of approval.

12 USA Key Figures Population: 314,519,000 Population over 65: 41,831,027 # Reported Afib Cases: 2,200,000 Ablating EPs: 1,489 Afib Ablations performed last year: 10,000 The USA has the largest number of ablating EPs, as well as a large number of Afib cases. However, the USA has had less ablations performed last year than the EU and India.

13 FDA Approval Process Implement QMS, Submit Pre-IDE, create clinical trial protocols Once Pre-IDE is approved, conduct clinical trials Submit PMA with clinical data, pay PMA fee FDA reviews PMA within 180 days, conducts facility inspections, issues approval letter Pay annual registration fee, subject to random FDA inspections Will include two trials, proof of concept in man (30-60 patients) and the pivotal trial ( patients) Key Figures Time to approval: 5-11 years Size of Pivotal Trial: patients Estimated Cost: $5,000,000 - $10,000,000 PMA Letter of Approval

14 USA Regulatory Analysis FDA approval is the longest and most expensive approval process we analyzed. This is largely because of the scope of clinical trials normally required. The FDA has recently come under criticism for it s increasing response times, poor electronic infrastructure, and unwillingness to adopt international standards. Despite these drawbacks, FDA clinical trials are very extensive making them widely accepted internationally. High cost and long approval make seeking FDA approval and the CE Mark concurrently very difficult.

15 South Korea Key Figures Population: Population over 50: 5,950,528 South Korea does not have a large amount of doctors available given its population. # Reported Afib Cases: 16945

16 KFDA Approval Process Register a Korean License Holder, submit SER technical file Submit device to Korean Testing lab for type testing, KFDA reviews SER technical file Obtain a product license, Korean License Holder must be shown to be in compliance with Korean Good Manufacturing Practice Korean license holder must present documents when importing medical devices. Certificates valid for three years Accepts a wide range of clinical data from pre-approved sources. Korean License Holder must possess a KGMP license and Certificate of Product Approval audited by KFDA and a third party on premise at all times

17 Korean Regulatory Analysis The Korean approval process considers clinical data from any OECD member country. The South Korean regulatory liaison plays a major role in the approval process. Key Figures Time to approval: 6-8 months Size of Pivotal Trial: 100 patients Estimated Cost: $500,000 - $1,000,000 KGMP License Certificate of Product Approval South Korea has one of the lowest concentrations of doctors amongst developed nations, making efficiency and time-saving technology critical. South Korea is currently creating a 4 tier classification scheme, the Circumblator may fall within class 3 or 4 depending on the new regulations.

18 Australia Key Figures Population: 21,662,093 Population over 50: 314,921 # Reported Afib Cases: 400,000 Ablating Eps: 6 Research on Atrial Fibrillation is fairly new for Australia. Australia is currently becoming more knowledgeable in Atrial Fibrillation and more research is being done to help diagnose and treat. Afib Ablations performed last year: 324

19 TGA Approval Process Implement ISO:13485:2003 Submit a design dossier to TGA Appoint a sponsor, sponsor's name must appear on all labeling Through sponsor, register device in the GMDN database TGA issues Certificate of Inclusion, yearly renewal fee Key Figures Time to approval: 3-6 months Size of Pivotal Trial: patients Estimated Cost: $2,000,000 - $3,000,000 Certificate of Inclusion GMDN Registration

20 Australian Regulatory Analysis One of the most standardized regulatory processes, TGA approval is recognized in the EU, Switzerland, Canada, New Zealand, and Singapore TGA may act as a Notified Body

21 Brazil Key Figures Population: Population over 50: 13,770,228 # Reported Afib Cases: Brazil has been developing their incorporation of medical devices quite rapidly, having one of the highest approval rates for Class 3 devices. # Cardiologists: 8000

22 ANVISA Approval Process Appoint a Brazilian Registration Holder, must possess a Company Working Allowance Submit device for INMETRO electrical safety testing, proof of compliance with RD/59/00 and RDC 25/2009 Submit technical file, need for clinical trials determined by ANVISA Submit Certificate of Free Sale and Letter of Authorization to BRH to be notarized ANVISA reviews forms and assigns a registration number, must be renewed every five years Key Figures Time to approval: 6 months Size of Pivotal Trial: patients Estimated Cost: $1,600,000 - $2,400,000 INMETRO Certification Certificate of Free Sale Letter of Authorization

23 Based large portions of regulatory process on FDA guidelines One of the highest approval rates for class 3 devices High risk devices in use elsewhere may require an Economic Information Report Increasingly popular location for clinical trials Brazilian Regulatory Analysis

24 Canadian Market Key Figures Population: 34,938,400 Population over 50: 12,381,500 Reported Afib Cases: 350,000 Ablating Eps: 10 Senior citizen are among the fastest growing populations in Canada and this age group is expected to continue growing for the next several decades. 1 Afib Ablations performed last year: 1,430

25 Health Canada Approval Process Implement ISO:13485:2003 Prepare Medical Device License application, conduct pre-market review Once approved, device is legal for sale, manufacturer subject to a yearly fee and audit Pursue a Private Label Medical Device License with Health Canada Clinical data from other countries accepted. Key Figures Time to approval: 6 months Size of Pivotal Trial: patients Estimated Cost: $3,000,000 - $4,000,000 MDEL Certificate ISO13485;2003 Certificate

26 Canada does not require an in-country liaison Canada places a large importance on the role of the manufacturer, AMI falls under this definition Obtaining a PLMDL greatly helps with distribution, overcoming one of the largest issues with selling in Canada Canadian Regulatory Analysis

27 Japan Key Figures Population: 127,520,000 Population over 50: 25,504,000 # Reported Afib Cases: 2,083,677 Ablating Eps: 60 Afib Ablations performed last year:47 Japan has the highest proportion of elderly citizens, more than 20% are over the age of 65. Japan s life expectancies have been the highest in the world for many consecutive years

28 PMDA Approval Process Appoint marketing authorization holder (D-MAH), submit application for foreign manufacturers accreditation Demonstrate ISO13485, Pre-Market Approval application, and design dossier in STED format Pass QMS inspection by PMDA Key Figures Time to approval: 5 years Size of Pivotal Trial: patients Estimated Cost: $5,000,000 - $6,000,000 Pre-Market Approval Certificate PMDA issues Pre-Market Approval certificate

29 Japanese Regulatory Analysis Japan does not accept CE Mark or any other foreign clinical data Japanese regulatory process is nearly as long and difficult as the FDA s Although widely accepted elsewhere, the additional logistics of seeking approval in Japan are too expensive compared to CE Marking

30 India Key Figures Population: 1,210,193,422 Population over 50: 741,248,288 # Reported Afib Cases: 1,205,073 Ablating Eps: 20 Afib Ablations performed last year: 750 About 60 percent of the arrhythmia cases that occur in India have been Atrial Fibrillation cases. India has a great amount of cardiologists but the number of electrophysiologists is fairly low.

31 Indian Approval Process Appoint Indian Authorized Agent to act on your behalf, must have a valid wholesale license Submit Form 40 for device registration Identify distributor and apply for an import license using forms 8 and 9 Certificates valid for 3 years Key Figures Time to approval: 9 months Size of Pivotal Trial: patients Estimated Total Cost: $500,000 - $1,000,000 Registration Certificate Form 41 Import License Certificate Form 10

32 Indian Regulatory Analysis Places a high value on the status of home country approval The India Authorized Agent must be a resident of India and be a medical professional Form 10/41 reapplication process identical to initial application Currently establishing a streamlined regulatory process and device classification. India s decentralized and regional nature will require multiple distributors

33 Chinese Market Key Figures Population: 1,347,350,000 Population over 50: 294,833,158 # Reported Afib Cases: 1,341,649 Ablating Eps: Unknown Afib Ablations performed last year: Unknown China has an aging population and the number of Atrial Fibrilation cases is projected to increase in the future. Though Electrophysiologist data is unavailable the population size and age depicts a need.

34 SFDA Approval Process Appoint legal agent and after sales agent Submit proof of compliance with ISO13485, any foreign marketing approval certificate, and technical files Submit Chinese Registration Standard document to SFDA Key Figures Time to approval: 6-9 months Size of Pivotal Trial: patients Estimated Cost: $600,000 - $1,200,000 IMDRC Certificate SFDA issues IMDRC, valid for four years

35 Requires country of origin clearance Reputation for unannounced delays especially during device classification process May request additional clinical data, this data must be collected within China Chinese Regulatory Analysis

36 Regulatory Approach Due to high costs and relatively long approval times compared to other nations, EU, US, and Japanese approvals are usually sought after in series. A device with approval for sale in one of these markets will possess enough clinical data to make approval in other large markets simpler and faster. With a CE Mark, access to several large markets such as Canada, India, South Korea, Australia, and Brazil can follow with little time delay and only regulatory expenses (as clinical trials should not be needed).

37 Questions?