This document discusses the regulatory pathway for MIGS devices in the United States. It outlines how the requirements for MIGS device approval through the PMA process have evolved over time based on learnings from early studies. Specifically, it notes that sample sizes, follow-up periods, clinical endpoints, and trial methodology have all increased in rigor. This includes moving primary endpoints from 12 to 24 months, requiring terminal washout periods, and measuring diurnal intraocular pressure. The document emphasizes that achieving level 1 clinical evidence for approval requires significant effort and collaboration between industry and the FDA over many years.

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The MIGS Regulatory Path
under the lens..
Sean Ianchulev, MD MPH
Clinical Associate Professor, UC San Francisco

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Sean Ianchulev, MD MPH
Clinical Associate Professor, UC San Francisco
Disclosures:
Chief Medical Officer, Transcend Medical (acquired by Alcon 2016)
Partner, PME Ventures
Board Member: Eyenovia, Kurobe, Iantech

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Stent Technology arriving to Ophthalmology
The Next Frontier
Neurovascular
Cardiovascular
Pulmonary
Gastrointestinal
Urological/
Gynecological
Peripheral Vascular
Ophthalmology
MIGS

4. Before 2000
Tube Trab
Glaucoma Surgical Options

5. 2010
Glaucoma Surgical Options

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MIGS LANDSCAPE ten years later….
• Innovation returns to glaucoma surgical treatments
• MIGS is establishing a new frontier in surgical glaucoma
• Strong pipeline of MIGS devices on the horizon
• Transformative innovation enabled by:
• Clarity of the regulatory PMA/510K process
• Strong clinical and regulatory science & development framework
• Prospective stability/predictability of the regulatory pathway

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The beginning of the MIGS PMA
• First MIGS PMA study: 2005-2010 (iStent®, N240+)
• First MIGS Approval: 2012 (iStent®)
• Second MIGS PMA study: 2009 -2015 (CyPass®, N505)
CyPass®iStent®
2005 2009 2016

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iStent®
2005 2009 2016
What changed?
1. Change in size of recommended PMA validation trial
2. Change in recommended endpoints
3. Change in clinical trial methodology
CyPass®

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Sample Size:
• Randomized subjects – 2X the original (240500+)
• Enrollment can total N 900 (screen failures from wash-out)
N = 240
COMPASS trialN = 505
iStent® trial
N = 276 ABC trial
N = 212 TVT trial
N = 255 EMGT trial

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Follow-up & Clinical Outcomes Measurement
• Primary endpoints for efficacy: 24 months (12 months if justified)
• Safety Follow-up : 24 months
• Terminal wash-out required: 12 and 24 months
• Diurnal IOP measurement post-washout at B/L, 12 and 24M

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How it changed?
1. Learning on both sides: FDA and industry
2. Workshops, ANSI, FDA guidance
3. Tremendous effort on all sides
The Effort: Stories from the Transcend Reg. Dept.
1. COMPASS protocol version P (n=16)
2. 7+ years of constant exchange with the FDA
3. 7,000+ pages of correspondence and submissions

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Terminal Wash-out
Primary EP
Sample Size
The Bottom Line:
It takes hard work for Level 1 clinical evidence and validation….
Diurnal IOP
Strict Meds Rescue Criteria
240+
12M
NO
NO
NO
505+
24M
YES
Yes
Yes
BEFORE AFTER

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IT is a PMA World:
The age of the PMA highway vs the 510K alley..
Stand Alone
REFRACTORY
510K
Stand Alone
NON-REFRACTORY
PMA
Phaco Combo
NON-REFRACTORY
PMA
Stand Alone
NON-REFRACTORY
PMA

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Today: it’s easy.....(right?!)
Just follow the guidance....