(HDE) and Breakthrough Devices Program

Overview of Humanitarian Device Exemption (HDE) and Breakthrough Devices Program Tieuvi H. Nguyen, Ph.D. Chief Intraocular and Corneal Implants Branch Division of Ophthalmic and Ear, Nose, and Throat Devices ODE/CDRH/FDA

Financial Disclosure The author does not have financial interest in this presentation

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21st Century Cures Act • Legislation Passed: December 13, 2016 • Specific Provisions in the Act: – Sec. 3052: Changes to existing Humanitarian Device Exemption (HDE) Program – Sec. 3051: Moved “Priority review” program to “Breakthrough” program • Can also apply to 510(k) and DeNovo

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HDE Application •Marketing application to FDA (CDRH, CBER) for a device classified as a Humanitarian Use Device (HUD) –Est. 1990: Designed to encourage the development of devices intended for rare diseases

•Class III Medical Device •HDE approval authorizes legal marketing of an HUD 4

HDE Application Process Demonstrate that you meet the criteria for HUD

Step 2: After HUD is granted, submit an HDE application to CDRH/CBER

Step 1: Obtain designation of the device as a HUD from FDAs Office of Orphan Products Development (OOPD)

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Eligibility for HDE 1. device (with intended use) must have received HUD designation AND 2. there is no comparable device currently legally marketed in the United States • may have more than one approved HDE for the same intended use • HDE approval expires with subsequent approval of PMA

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HUD Definition A Humanitarian Use Device (HUD) is a medical device intended to benefit patients in treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 individuals per year in the United States. not more than 8,000 21st Century Cures Act Amendment to regulation published June 7, 2017 7

HUD Designation • Prevalence: – total number of patients with a disease or condition in the population at a given time (e.g., point prevalence)

• Incidence:

≤ 8,000 individuals

– number of new patients diagnosed with a disease or condition during a particular time period (e.g., annual incidence) 8

Population Estimate • Is used to measure annual incidence • Determines eligibility of a patient population (intended use) and device for a Humanitarian Use Device • Definition is similar, with some slight differences, among different categories of devices and patient groups. 9

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Population Estimate: Therapeutic Devices Number of: • new patients, per year • diagnosed with the relevant disease or condition • potentially eligible for treatment with the device

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Population Estimate: Diagnostic Devices Number of: • new patients, per year • subjected to diagnosis with device, regardless of test result (e.g., positive, negative) May be ineligible for HUD designation even if device diagnoses rare disease or condition (e.g., newborn screening).

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Population Estimate: Devices for Repeat or Multiple Use Number of: • new patients • who would be eligible for, or subjected to, the device in a given year • not on the total number of expected uses of a device in a given year by all patients.

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HDE Approval Safety – –

does not pose unreasonable risk of illness or injury same threshold as PMA devices

Probable benefit – outweighs the risks of using the device, taking into account the probable risks and benefits of alternative therapies – exempt from effectiveness – different from PMA devices (reasonable assurance of effectiveness) – 21st CC - Mandated a draft guidance document defining

criteria for establishing probable benefit within 18 months 13

Limitations of HDE Approval • IRB approval is required before the HDE-approved device is used –except in emergency situations

• Labeling – must clearly identify device as an HUD – must state effectiveness for that indication has not been demonstrated

• Profit Restrictions –HDE may not be sold for profit (with exception)

21st Century Cures Act Removed requirement that reviewing IRB be “local” National IRBs may now approve HDE use

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Exception to Profit Restrictions Eligible to be sold for profit if device meets one of the following criteria regarding treatment/diagnosis of disease: 1. Occurs in pediatric patients or in a pediatric subpopulation 2. Does not occur in pediatric patients at all (e.g., Alzheimers)

3. Development of the device for pediatric population is impossible, highly impracticable, or unsafe.

Determination based on disease and HDE device label 15

Annual Distribution Number (ADN) • the specific number of devices that may be distributed for profit, per year ADN Calculation: # of devices reasonably needed to treat, diagnose, or cure an individual per year

X

8,000 16

Ophthalmic HDE Approvals Argus II Retinal Prosthesis System (H110002)

INTACS® Prescription Inserts For Keratoconus (H040002)

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BREAKTHROUGH DEVICES PROGRAM 18

Collaboration Perceived Barriers & Interaction!

Patient access!

FDA approval

Marketing application Pivotal study

Feasibility study

Preclinical testing

Device prototype Device concept Patient need 19

Breakthrough Devices Program History Priority Review Nov. 21, 1997

FDA’s EAP Final Guidance April 13, 2015

2015

Section 202 of FDAMA Requirement of priority review for devices whose approval is expected to provide significant public health benefits

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Century Cures Act Dec. 13, 2016

2016

2017

Breakthrough Devices Program Draft Guidance October 25, 2017

2018

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Breakthrough Devices Program

• Supersedes Priority Review Program  Statutory criteria for granting priority review and outlined standard procedures to achieve an efficient review process • Supersedes EAP  Adds 510(k)s • Elimination of EAP requirement  Removed requirement of Device Development Plan (DDP) from EAP

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Criteria More effective treatment or diagnosis of life threatening or irreversibly debilitating disease + At least one of the following: Represents breakthrough technology No approved or cleared alternatives exist Offers significant advantages over existing approved/cleared alternatives Availability is in the best interest of patients (e.g., addresses an unmet medical need) 22

Benefits of Breakthrough Device Designation ✓ Interactive and timely communication during development & review • Between submissions and during open submission review • Review team support • Senior management engagement ✓ Prioritized review ✓ Efficient and flexible clinical study design ✓ Enhanced opportunity for pre/ post-market balance of data collection for PMA devices ✓ Opportunity for reduced manufacturing information in a PMA

CDRH Ophthalmic Devices 3 Breakthrough Designations Granted in past 6 months

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Breakthrough Device Process Designation Request Q-Submission - Applicant provides device description, proposed indication, rationale for meeting statutory eligibility criteria - 60 day review clock

Follow On Q-Submissions - Data Development Plan collaboration (optional) - Requests for feedback similar to Pre-Submissions (highly interactive, prioritized review)

- Regular status updates in between submissions

IDEs and Marketing Submissions for Granted Breakthrough Devices - Prioritized review, senior management involvement - Potential to accept greater uncertainty for approval with the possibility of post-market data component

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Regulatory Approaches to Promote Innovative Devices

Innovative devices beingback developed forpatient a wide variety of life It all are comes to the threatening or irreversibly debilitating conditions We are using our regulatory tools and pathways to support bringing innovative devices to market • Breakthrough Devices Program • Early Feasibility Studies • Real World Evidence • Patient Perspectives/ Patient reported outcomes 25

Questions Tieuvi Nguyen, Ph.D. [email protected] 301-796-6860

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