Regulatory Problems Moderators: Eugene Chen and Michael Kochman, MD

IRB No shopping Non-approved use – Local use or trial – Industry marketing claims

Pathways Humanitarian Device Exemption – Less than 10,000 patients Recoup R&D in US – OK for non-US profit Requires IRB approval Retrospective data analysis allowed

IDE No FDA approval needed for clinical trial Significant risk vs. Non-significant risk – If IRB determines significant risk, then FDA approval required Likely path for NOTES® – Exemption to allow for clinical use – Requires clinical trial End-points defined Outcomes If primary end-point fails, trial redo required

Pathways PMA – Clinical trials 510-K (predicate device) – Starting to ask for clinical data Safety Efficacy – new issue

510(k) Letter to file – Minor change documentation Special Standard

Non-US CE – Industry migration to Europe – Individual device use if made in-house with IRB – Industry or multicenter requires exclusion to CE Individual can obtain CE (similar to 510(k)) ISO 9001 equivalent – independent body certifies adherence to standards – (balloons would require PMA, but CE approved) – Device authorities vary by country as far as sales – EU notified body » 72 days

Non-US Canada Japan

International Cross-Talk Details lacking in published studies – Useless for FDA purposes

FDA Branches – Regulatory – Compliance/enforcement Question studies sponsored for non-label indications Concerns re: hidden specific indications Black-box “not indicated for…” eliminating “hidden specific” indications External reviewers

MD Lack of clear understanding Confusion re: label indications

Pathways 510(k) – Tools – Endoscopy PMA ($90 million US or so) – Implants – May have a formal reclassification to predicate device

Current Issues Pathways not clear – What makes a 510(k) or a PMA not uniform – Surgical branch and GI/GU branch NOTES and obesity are going to GI/GU and asked to be PMA Industry has tried 510(k) sneaks International differences Broad claims vs. specific claims – Revenue and marketing issues Innovation in US stifled by process and regulation – Leadership lost – Economic impact

Degree of Impact on Adoption of NOTES® Significant – Slow-down – Non-US development

Source of Problem Non-statute interpretation of regulation Claims

Parties Affected Physicians Industry Patients

NOSCAR® Taking device forward is difficult for professional societies – Can we take and obtain device approval as a retractor for TV chole? Support 510(k) for a company and device Different access site is viewed as PMA – NOSCAR to go forward saying FDA cannot regulate surgical/clinical practice Position statement on safety – Transvaginal access statement needed – Trochar placement irrelevant Eliminate statement on registry

Priorities FDA pathways in US need clear definition and alignment – Engagement on multiple levels – One group to handle space – Likely congressional engagement International homologation – Studies not informative, ergo, not useful in current iterations

Priorities (cont.) Professional society interaction – May be best to avoid industry queries on record – Need to push back on regulation of procedures Access site, target (including endoluminal) not in purview of FDA – Regulatory strategy alignment Reiterate corporate mission support – Guideline statement on transvaginal (TV) access as accepted clinical use TV cholecystectomy as accepted – Guideline statement on flexible endoscope use in peritoneal cavity is accepted clinical use