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Poster Presentation - FDA Compliance Landscape & What it Means to Your AI Aspirations

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CitiusTech delivered a poster presentation on the FDA compliance landscape (PMA, De Novo, 510k and Pre Cert) and its implication on AI in Healthcare, at the Mayo Clinic AI Symposium earlier this year.

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Poster Presentation - FDA Compliance Landscape & What it Means to Your AI Aspirations

  1. 1. FDA Compliance Landscape (PMA, De Novo, 510k and Pre Cert) & What it Means to Your AI Aspirations Fernando Schwartz, Vice President - Data Science & Consulting, CitiusTech The FDA categorizes medical devices into one of three classes – Class I, II, or III – based on their risks and the regulatory controls necessary to provide a reasonable assuranceof safety and effectiveness.  Class I and II devices generally pose the lowest risk to the patient and/or user can undergo 510(k) premarket notification process  Class III devicespose the highest risk subject to Premarket Approval (PMA) process Premarket Approval (PMA) Most stringent regulatory category for medical devices Applies to Class III devices. Dueto the level of risk associated with Class III devices, they require a Premarket Approval (PMA) application under section 515 of the FD&C Act in order to obtain marketing clearance. De Novo Compliance Less stringent compared to PMA pathway, specially targeted for devices which do not have a valid predicate Applies to Class I or Class II devices for which general controls or general and special controls provide a reasonable assuranceof safety and effectiveness. 510(k) premarket notification process Most common regulatory path to market for medical devices To market a Class I, II, and III device intended for human use, for which a PMA is not required, must submit a 510(k).) Precertification (Pre-Cert) Most stringent regulatory category for medical devices The Software Precertification (Pre-Cert) Program is envisioned as a voluntary pathway that embodies a regulatory model more tailored than the current regulatory paradigm to assess the safety and effectiveness of software technologies without inhibiting patient access to these technologies. It aims to evaluate necessary information at different points in the product’s lifecycle, to establish a reasonable assurance of safety and effectivenessfor the product. Premarket Approval (PMA) Overview and Types A Premarket Approval (PMA) application is a scientific, regulatory documentation to FDA containing below information in addition to administrative elements -  Technical Sections: The technical sections containing data and information should allow FDA to determine whether to approve or disapprove the application  Non-clinical Laboratory Studies Section: Non-clinical laboratory studies section includes information on microbiology, toxicology, immunology, biocompatibility, stress, wear, shelf life, and other laboratory or animal tests. Non-clinical studies for safety evaluation must be conducted in compliance with 21CFR Part 58  Clinical Investigations Section: Clinical investigations section includes study protocols, safety and effectiveness data, adverse reactions and complications, device failuresand replacements, patient information, patient complaints, tabulations of data from all individual subjects, results of statistical analyses, and any other information from the clinical investigations Tradi�onal PMA Modular PMA Streamline PMA Product Development Process (PDP)  21 CFR 814.20(b)  PMA filing criteria is a 2 step process: Acceptancereview (15days) and filing review (45 days)  GMP: FDA will inspect the site  Timeline: 180 days  Submit documents in different modular stages  Need prior plan for modular PMA before reaching to FDA  Timeline: 90 days for each module and 180 days after final module  Use for known technologies with known disease processes  Already 2-3 approved PMA for similar types must be present  GMP: Inspection is deferred if FDA has completed inspection within past 2 years  Timeline: 180 days  PDP is a combination of IDE and PMA (FD&C Act Section 515F)  Not very popular  Timeline: 120 days after completion of clinical study Types of PMA De Novo Compliance Process Step 1: Pre-Submission: Available for sponsors and manufacturers to obtain regulatory feedback  Topics that may be addressed using the Pre-Sub process include, but are not limited to - o Specific preclinical performance testing required to support pre-market clearanceor approval application. o The appropriate regulatory path for a novel device, such as the 510(k) route or a de novo application. o The formal designation of a device clinical study as either "significant risk" (SR) or "non-significant risk" (NSR).  Request a Pre-Sub meeting with FDA - o Cover Letter o Thorough description of medical device o Mechanism of action on the body o Technical characteristics of device -AI/ML, etc. o Planned testing strategy o Queries to be asked to FDA Step 2: Submission of De Novo  Submission of FDA 513(g) if no clear predicate can be established - o “Request for Information” - outline the characteristicsof your device and include rationale on why it falls into a specific class. In 60 days FDA will issue classification with suitable regulation number and product code.  New Devices De Novo - o New devices will automatically fall into Class III. However, not all devices are high risk. Submit a De Novo request and in 120 days FDA will determine Class I or II for device and may issue an entirely new product code and regulation number. Step 3: Granting of De Novo  The specific device and device type is classified as Class I or Class II. The device may then be marketed immediately and served as a predicate device. FDA 510k Decision Making Process for Approval 510(k) Compliance Overview and Types  510(k) compliance is necessary to market a Class I, ClassII, and III device(s) in US - o Intended for human use o Premarket Approval(PMA) is not required  A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective (substantially equivalent) to a legally marketed device (21 CFR 807.92(a)(3)) that is not subject to PMA  Submitters must compare their device to one or more similar legally marketed devices and make, support their substantial equivalenceclaims Workflow: Types of 510k Compliances Tradi�onal 510k Abbreviated 510k  21 CFR 807  Used for any original 510k or for a modification to a previously created device under 510k  Submitted when a guidance document exists  A special control has been established or FDA has recognized a relevant consensus standard Special 510k  Maybe submitted for a modification to a device which does not affect intended use or does not alter fundamental scientific technology  Device modification is mostly around design control  No data is evaluated by FDA (Declaration of Conformity – Conformance Assurance Pre-Cert – How it’s different from Traditional Pathway Pre-Certification Process Which Compliance to Use PMA De Novo 510k When To assure the safety and effectiveness of Class III devices. Novel devices of low to moderate risk (Class I and II). Class I, II, and III device intendedfor human use, for which a Premarket Approval (PMA) is not required. Device Class 3 Class 1 and 2 Class 1, 2 and 3 Why Due to the level of risk associated with Class III devices, FDA has determinedthat general and special controls alone are insufficientto assure the safety and effectiveness of Class III devices. Therefore, these devices requirea premarket approval (PMA) application under section 515 of the FD&C Act in order to obtain marketing clearance. Do not have a valid predicate device. To demonstrate that the device to be marketed is at least as safe and effective (substantiallyequivalent)to a legally marketed device that is not subject to PMA. Submitters must compare their device to one or more similar legally marketed devices (predicates) and make and support their substantial equivalencyclaims. Risk Factor The manufacturer must prove that the risk factor presentedwith this device is a medium risk. The manufacturer must prove that the risk factor presentedwith this device is a medium risk. The manufacturer must merely prove that the risk presented by the device is no greater than its substantial equivalence device. Complexity Most Stringent Moderate Least Stringent Timeline 180 days 120 days 90 days Submission Cost Std Fee - $322,147 Small Business Fee - $80,537 Std Fee - $96,644 Small Business Fee - $24,161 Std Fee - $10,953 Small Business Fee - $2,738 Example GuardianConnect System Contact (Viz.ai) Icobrain FDA Compliance Landscape Pre-Submission (OPTIONAL) Submission of De Novo Request No existing active submission for same device, information provided to determine whether a potential predicate device exists, and proposed special controls provided (if proposed as class II device) FDA Classification Review Decline De Novo Request : PMA Required OR Discuss Reclassification under 513(e) or 513(f)(3) Likely predicate, class III regulation or approved PMA for same device type exists? Decline De Novo Request : Submit 510(k) (unless 510(k) exempt) FDA Substantive Review Additional information (AI) needed to complete the substantive review? De Novo Request placed on hold, request AI Requirements for class I or class II met? Grant De Novo Request; device may be legally marketed De Novo Request placed on hold submitter notified of issue(s) to be resolved Yes, class III regulation or approved PMA Yes, likely predicate No Yes Yes No Decline De Novo Request : PMA or New De Novo Request Required No No Yes <= 120 FDA calendar days to Grant/ Decline Identify the new device and predicate device Decision 1: Is the predicate device ally marketed? Decision 2: Do the devices have the same intended use? Decision 3: Do the devices have the same technological characteristics? Review design, materials, energy source and other features of the devices. Review all labelling and assure that it’s consistent with IFU statements No No No Yes Yes Yes Yes SE NSE NSE NSE Determine the questions of safety and effectiveness the different technological characteristics may raise Decision 4: Do the different technological characteristics of the devices raise different questions of safety and effectiveness? Decision 5a : Are the methods acceptable? Review the proposed scientific methods for evaluating new / different characteristics’ effect on safety and effectiveness Decision 5b : Does the data demonstrate substantial equivalence? Evaluate performance data No SE Yes No NSE NSE NSE Yes Traditional Approach Pre-submission Document Administrative Review Clinical Evaluation FDA Review Feedback for Safety Go-To-Market Expected Timeline – 90-180 Days, as review, interaction, feedback starts after pre-submission of document with product information and intended usage 90-180 days Pre-submission Document Interac�ve Review Period Go-To-Market and Post-Market Surveillance (RWD) Pre-Cert Program Approach Expected Timeline – 20-25 days, as review, interac�on, feedback starts before pre-submission of document with product informa�on, intended usage, clinical evalua�on result, organiza�onal appraisal process, and feedback review and comments 20-25 Days Excellence Determination (Mandatory Step) Real World Performance (Mandatory Step) Review Determination (Mandatory Step)  Develop premarket review framework based on risk of the product  Pre-submission document covers information of each element of SaMD  KPI and metrics designed across five principles to gauge quality – Product Quality, Patient Safety, Clinical Responsibility, Cybersecurity and Proactive Culture  Collect post launch data from diverse sources  During stage 1, all organizations are supposed to showcase capability for RWP (post surveillance)  Run three major analytics – real world health analytics, user experience analytics, and product performance analytics Pre-9102margorPtoliPnoitacifitreC 1 Streamlined Premarket Review (Mandatory Step for High Risk Device)  FDA conducts this review based on previous feedback  Identify requirements for premarket review  Analyze safety and effectiveness of product to assure it further 2 3 4

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