Premarket Notification: A Key Element of US Medical Device Regulation Presented by Philip J. Phillips IOM Workshop Public Health Effectiveness of the FDA 510(k) Clearance Process Washington, D.C., June 14, 2010
Goals 1. Provide objective information on today s 510(k) program on which IOM can draw conclusions and formulate recommendations 2. Ensure that the complexities of the regulatory system are not overlooked in the process 3. Contribute to regulatory reform that results in reasonable premarket review that encourages innovation, promotes and protects public health and achieves an optimum premarket/postmarket balance 2
Outline I. The Breadth of FDA Responsibility II. Safety & Effectiveness III. Device Classification IV. Premarket Notification a. Substantial equivalence b. Scientific integrity of the process c. Strengths, weaknesses and flexibilities V. Comparison: 510(k) v. PMA VI. Environmental Considerations VII. Closing Remarks 3
The Breadth of FDA Responsibility Not merely tongue depressors to implantable defibrillators General purpose articles Device components, parts and accessories Custom devices Devices resulting from - Reprocessing of OEM single use disposable devices - Remanufacturing of durable medical equipment The system of identifying generic types of devices and classifying them is an efficient means to allocate FDA resources and maximize FDA s impact on public health. 4
Safety & Effectiveness Considerations Intended patient population Conditions of use in labeling or advertising Balance of health benefits to risks from use Reliability of the device Reasonable assurance of safety Probable benefits derived from use outweigh probable risks; and absence of unreasonable risk of illness or injury Reasonable assurance of effectiveness 5 Clinically significant results in a significant portion of the target population
Foundation for Premarket Notification The approach to assuring S&E varies by the particular device s classification Classification determines the nature and degree of FDA regulation Class I (general controls) Class II (performance standards/special controls) Class III (premarket approval) Premarket notification (510(K)) is the general control that determines the classification of new devices 6
Classification - Generic Type of Device Generic type of device means a grouping of devices that do not differ significantly in purpose, design, materials, energy source, function, or any other feature related to safety and effectiveness, and for which similar regulatory controls are sufficient to provide reasonable assurance of safety and effectiveness. Currently there are >1800 generic types of devices that are the subjects of classification regulations 7
The Formation of Today s 510(k) Program Initial comparisons were easy; little apparent differences between the old and new Concept of SE was quickly challenged Mandatory performance standards could not be developed for class II devices Differences between new and old became more pronounced (intended use and technology) Any measurable shift toward PMA process threatened to drain FDA resources SE evolved to compensate for regulatory realities 8
Substantial Equivalence A device is substantially equivalent if, in comparison to a predicate, it: has the same intended use as the predicate; and has the same technological characteristics as the predicate; or has the same intended use as the predicate; and has different technological characteristics and the information submitted to FDA; - does not raise new questions of safety and effectiveness; and - demonstrates that the device is at least as safe and effective as the legally marketed device. 9
The Meaning of Intended Use Refers to the objective intent of the persons legally responsible for the labeling of devices (21 CFR 801.4) defined for postmarket purposes, not 510(k) In the context of 510(k), the scope is narrower Aspects of intended use of significance include the indications for use, Rx v. OTC distribution and whether the device is for reuse v. SUD Changes in indications for use - Present the biggest regulatory challenges - Agency decisions are the most difficult to explain 10
Intended Use (continued) For PMA devices, indications for use refers to the disease or condition, including the patient population for which it is intended For 510(k) devices, indications for use may also be functional in nature, i.e., what the device does Changes in indications for use, 2 varieties - Expansions in patient population e.g., cardiovascular diagnostic catheters proposed for cardiac ablation procedures - General to specific use (or vice versa) e.g., CO2 lasers labeled for photocoagulation, cutting and ablation of soft tissue proposed for tattoo removal 11
Intended Use (continued) Our recommendation: consider the following definition to understand FDA s 510(k) approach to intended use In the context of 510(k), intended use is a regulatory concept that determines the boundaries of use for a generic type of device and is constructed to encompass the widest breadth of use where the regulatory controls for the device type continue to assure S&E. 12
Lumenis, Ltd. C02 Laser (K100415) Cleared April 14, 2010 for vaporization, incision, excision, ablation or photocoagulation of soft tissue in 9 surgical specialties Let s examine one specialty area: Dermatology The AcuPulose laser is indicated for use in dermatorlogy and plastic surgery for the following applications: Ablation, vaporization, excision, incision, and coagulation of soft tissue in the performance of : Laser skin resurfacing Laser dermabrasion Laser burn debridement Laser skin resurfacing (ablation and/or vaporization) for the treatment of : wrinkles, rhytids and furrrows (including fine lines and texture irregularities). Laser skin resurfacing (ablation, and/or vaporization) of soft tissue for the reduction, removal, and/or treatment of: - Keratoses, including actinic and seborrheic keratosis, seborrhoecae vulgares, sebborhecfi wart and verrut seborrheica - Vermillionectomy of the lip - Cutaneous horns - Solar/actinic elastosis - Cheilitis, including actinic cheilitis - Lentigines, including lentigo maligna or Hutchinson s malignant freckle - Uneven pigmenmtation/dyschromia - Acne scars - Surgical scars - Keloids, including acne keloidalis nuchae 13 - Hemangiomas (including Buccal, port wine, a d pyonenic granulomas/granuloma pyogenicum/granuloma telangiectaticum) - Tatoos - Telangiectasia - Removal of small skin tumors, including periungual (Koenen) and subungual fibromas - Superficial pigmented lesions - Adenosebaceous hypertrophy and sebaccrous hyperplasia - Rhinophyma reduction - Cutaneous papilloma (skin tags) - Milia - Debridement of eczematous or infected skin - Bramous and squamous cell carcinoma, including keratoacanthomas, Bowen s disease (Erythroplasia of Queyrat), and Bowenoid Papulosis (BP) lesions - Nevi, including spider, epidermal, and protruding - Neurofibromas - Laser de-epitheliazation - Tricoepitheliomas - Xanthelasma palpebrarum - Syringoma Laser ablation, vaporization, and/or excision for complete and partial nail matrixecomy Vaporization/coagulation of: - Benign.malignant vascular/avascularskin lesions - Moh s surgery - Lipectomy - Verrucae and seborrhoecae, vulgaris, including paronychial,, perungal and subungal warts Laser incision and/or excision of soft tissue for the performance of upper and lower eyelid blepharoplasty Laser incision and/or excision of soft tissue for the creation of recipient sites for hair transplantation
Technological Characteristics FDA s approach to differences in technology 1. Do the differences raise new safety or effectiveness questions? - If yes, device is NSE - FDA interprets as new types of safety and effectiveness questions to afford agency discretion in decision-making 2. Is the new device as safe and effective as the existing? - FDA asks, Can the risks inherent with the new technology be mitigated? - Note: This is not a S&E evaluation similar to PMA Example Wireless telemetry Technology poses no new types of S&E questions Performance testing and labeling requirements mitigate risks 14
Scientific Integrity of 510(k) For a new device having the same intended use and the same technological characteristics Descriptive data - all cases - Side-by-side comparison of designs with specifications Performance data -when descriptive data does not assure performance - e.g., biocompatibility of patient contacting materials (ISO 10993) and electrical safety (IEC 60601) For a new device with differences in intended use and technological characteristics 15 As above, plus performance data (bench, animal and clinical) to assess the differences and mitigate associated risks
Scientific Integrity of 510(k) (continued) New devices include devices that are modified by their manufacturers With devices, constant and rapid change is inevitable Major changes in intended use/device design changes that could significant affect S&E require FDA clearance; subject to the same scientific review standards Manufacturers must decide what changes require a new clearance within the confines of their quality system Integrity of the 510(k) process requires 1.verifying necessary submissions are filed; and 2.that all changes have undergone proper V/V 16
510(k): Strengths Weaknesses and Flexibilities Strengths Flexibility, e.g., freedom to apply knowledge from precedent Ability to grant exemptions (adjust agency priorities) Weaknesses Lack of device specific guidance and special controls Ability to address S&E issues with cleared devices Flexibilities 17 Opportunity to request needed information Ability to leverage the work of SDOs through the recognition of consensus standards for use in review 3 rd party review
Premarket Notification v. Approval First programs should not be compared 510(k) is a classification process PMA is a determination of S&E that leads to approval 510(k) Class I and II Substantial Equivalence S&E N.A. [S&E requires verification and vigilance] Unconditional Clearance Class III PMA Reasonable assurance of S&E S&E device-by-device, premarket conformance assessment Conditions for the TPLC FDA Approval 18
Environmental Considerations Competition, cost containment and the practice of medicine Environment factors prompt device differentiation Intended use and technology provide the means The result -regulatory challenges - Combination products (devices, drugs and biologics) - Software control, networked systems and inter-device compatibility - Issues with the device user interface (human factors) - IVD Multivariate Index Assays (IVDMIAs) - Reuse of SUDs FDA s regulatory system should anticipate change and promote product improvement 19
Closing Remarks Assuring that devices are safe and effective is a complex system of requirements, with 510(k) being one component The 510(k) process differs from how it is most frequently characterized concept of SE is misleading The 510(k) program has strengths and weaknesses, but it makes significant contributions to public health. Whether 510(k) is maintained as is, changed or abandoned, the system must be flexible enough to accommodate constant and rapid change, and have the integrity to withstand criticism; For FDA staff, making correct decisions is difficult enough without having the underlying regulatory process constantly under attack. 20