Introduction to US FDA CDRH Regulations, PMA

Transcription

1 Introduction to US FDA CDRH Regulations, PMA Do-Hyun Kim, Ph.D, Ph.D CEO, BT Solutions, Inc. South Korea CEO, Solutions 4BT, LLC, USA The Transformation of Medical Device Industry for Thailand 4.0: Software Validation for Medical Devices Novotel Bangkok Sukhumvit 20, 5th floor, Room Benjasiri 1-2 January 17, 2017, 3:45 pm 5:00 pm

2 Classification Class I Lowest Risk An example of a Class I device is a ma nual toothbrush. Class I devices are subject to general control s. Class II Moderate Risk Examples of Class II devices are mal e condoms and non-invasive blood pressure monitors. Class II devices are subject to general controls and special controls. Class III Highest Risk An example of Class III device is a he art valve. Class III devices are subject to general controls and premarket approval.

3 After Classification Premarket Submiss ion Premarket notification [510(k)] For Class I devices exempt from [510(k)] the submission of a [510(k)] and marketing clearance from FDA is not required. If your Class I (or certain class II) device is exempt, subject to the lim itations on exemptions, from the 510(k) process, this will be stated in the classification regulation. However, other General Controls such as registration and listing, labe ling, and good manufacturing practices (GMP) may apply. PMA

4 Premarket Approval (PMA) Original PMA Licensing Agreement PMA Modular PMA Some single use devices Premarket Report (PMR) Supplements Panel-track supplement: significant change 180-day supplement: significant change in material, soft ware, etc Real-time supplement: minor change in software, steriliza tion, etc 30-day notice: change in manufacturing procedure, etc

5 PMA (1): Traditional (Original) PMA A PMA application involves many volumes of material to be submi tted to FDA. Device description and intended use Nonclinical and clinical studies Case report forms Manufacturing methods Labeling, etc. In the traditional PMA method, the complete PMA application is s ubmitted to FDA at once. This method is generally used if the devi ce has already undergone clinical testing and has been approved i n a country with established medical device regulations.

6 PMA (2): Modular PMA In a Modular PMA the complete contents of a PMA are broken down into well -delineated components (or module) and each component is submitted to FD A as soon as the applicant has completed the module, compiling a complete PMA over time. The PMA is viewed as a compilation of sections or "modules," such as preclinic al, clinical, manufacturing, that together become a complete application. This method is recommended for products that are in early stages of clinical study. The process begins with a PMA Shell which lays out the plan for submission of the modules. The review team will work with applicants to develop a customiz ed shell for each specific product that includes module contents and suggeste d timelines. It is developed individually with the manufacturer for a specific de vice.

7 PMA(3): Premarket Report A Premarket Report (PMR) is a marketing application for Class III reprocessed single use devices (SUDs) that otherwise woul d have required a pre-market approval application. Among other information, a PMR must include validation dat a regarding cleaning, sterilization, and functional performance of the reprocessed device to ensure it is substantially equivale nt to a legally marketed device.

8 PMA(4): Licensing Agreement PMA A licensing agreement PMA involves a PMA applicant (licensor) en tering into a licensing agreement with another party (licensee) to provide that party with permission to reference the data in its PM A. The licensee, after submitting the licensing agreement PMA to FD A, may request FDA to approve its own device, by referencing all t he information that was used as a basis for approval of the licenso r s device. Upon receiving FDA s approval, the licensee assumes all the respon sibilities of a PMA applicant, including the manufacture and distrib ution of a device that is identical to the licensor s. In addition, foll owing approval of the licensing agreement, licensees may choose to make changes to their product. As for all PMA applicants, such changes may require the submission of a PMA supplement.

9 PMA(5): Panel-track supplements Supplement to an approved premarket application or premar ket report under section 515 that requests a significant chang e in design or performance of the device, or a new indication for use of the device, and for which substantial clinical data a re necessary to provide a reasonable assurance of safety and effectiveness.

10 PMA(6): 180-day supplements Supplement to an approved premarket application or premar ket report under section 515 that is not a panel-track supple ment and requests a significant change in components, mater ials, design, specification, software, color additives, or labeling.

11 PMA(7): Real-time supplements Supplement to an approved premarket application or premar ket report under section 515 that requests a minor change to the device, such as a minor change to the design of the devic e, software, sterilization, or labeling, and for which the applica nt has requested and the agency has granted a meeting or si milar forum to jointly review and determine the status of the supplement.

12 PMA(8): 30-Day Notices A notice under section 515(d)(6) that is limited to a request t o make modifications to manufacturing procedures or metho ds of manufacture affecting the safety and effectiveness of th e device. Product can be distributed after 30 days of notification, unles s it is determined inappropriate in 30days Where FDA finds such notice inadequate, FDA will inform the applicant that a 135-day PMA supplement or 75-day HDE sup plement must be submitted

13 PMA(9): Periodic (annual) reports Under section 212 of FDAAA, PMA applicants are subject to a n annual fee for periodic reporting concerning a class III devi ce.

14 Changes without a PMA Supplement (1) the change does not affect the device's safety or effective ness (2) the change is reported to FDA in a postapproval periodic r eport (annual report) required as a condition of approval of t he device, e.g., an editorial change in labeling which does not affect the safety or effectiveness of the device. Trivial changes, such as changes in the color of a label, would not have to be included in the postapproval periodic report

15 Product Development Protocol (PDP) Clinical evaluation of a device and the development of necessary i nformation for marketing approval are merged into one regulatory mechanism. Ideal candidates for the PDP process are those devices in which th e technology is well established in industry. The PDP allows a sponsor to come to early agreement with FDA a s to what would be done to demonstrate the safety and effectiven ess of a new device. Early interaction in the development cycle of a device allows a sponsor to address the concerns of the FDA bef ore expensive and time consuming resources are expended. A PDP that has been declared completed by FDA is considered to have an approved PMA ( ).

16 HDE An Humanitarian Use Device (HUD) is a device that is i ntended to benefit patients by treating or diagnosing a disease or condition that affects or is manifested in few er than 4,000 individuals in the United States per year. To obtain approval for an HUD, an humanitarian device exemption (HDE) application is submitted to FDA. An H DE is similar in both form and content to a premarket a pproval (PMA) application, but is exempt from the effec tiveness requirements of a PMA. The application, however, must contain sufficient inform ation for FDA to determine that the device does not po se an unreasonable or significant risk of illness or injury, and that the probable benefit to health outweighs the risk of injury or illness from its use. Additionally, the applicant must demonstrate that no co mparable devices are available to treat or diagnose the disease or condition, and that they could not otherwise bring the device to market.

17 IDE: Investigational Device Exemption Clinical evaluation of devices that have not been cleared for marketing requires: an investigational plan approved by an institutional review bo ard (IRB). If the study involves a significant risk device, the ID E must also be approved by FDA; informed consent from all patients; labeling stating that the device is for investigational use only; monitoring of the study and; required records and reports.

18 Foreign companies/studies Can a foreign company submit an IDE/Is a U.S. Sponsor required? A foreign company cannot sponsor an IDE; the company must have a U.S. agent who a cts as the sponsor (see 21 CFR (a)). The U.S. agent must fulfill all the responsibili ties of a sponsor identified in the IDE regulations. Do clinical studies have to be conducted in the U.S. / Will foreign studies be accepted? FDA will accept a foreign clinical study involving a medical device not conducted under a n IDE only if the study conforms to whichever of the following provides greater protectio n of the human subjects: the ethical principles contained in the 1983 version of the Declaration of Helsinki, or the laws and regulations of the country in which the research was conducted. When foreign clinical data is used to support a marketing application, the applicant sh ould ensure that the foreign data are applicable to the U.S. population and U.S. medica l practice, that the clinical investigators have recognized competence, and that FDA can validate the data through an on-site inspection or other appropriate means, if necessar y.

19 513(g) For devices that are innovative, it can sometime difficult to fin d an exact predicate device using the FDA classification datab ase. In this case, you can submit a 513(g) Request for Inform ation to the FDA. The 513(g) submission should outline the characteristics of your device and include rationale on why yo u believe it falls into a specific class.

20 Post-Market Regulations MDR (medical device reporting) Mandatory Medical Device Reporting: The Medical Device Reporting (MDR) regulation (21 CFR 803) contains mandat ory requirements for manufacturers, importers, and device user facilities to rep ort certain device-related adverse events and product problems to the FDA. Manufacturers: Manufacturers are required to report to the FDA when they le arn that any of their devices may have caused or contributed to a death or ser ious injury. Importers: Importers are required to report to the FDA and the manufacturer when they learn that one of their devices may have caused or contributed to a death or serious injury. The importer must report only to the manufacturer if t heir imported devices have malfunctioned and would be likely to cause or con tribute to a death or serious injury if the malfunction were to recur.

21 Other Post-Market Regulations Recalls Corrections Removals

22 PMA EXAMPLE

23 Original PMA Assume a CGM (continuous glucose monitor) Does not replace traditional glucose meter, but used as a supplementary A sensor implanted/attached to patient body continuously monitor the glucose level and transmits data to the console Only for 18-years gold and more

24 Submission (1) Cover letter Table of contents Mandatory User fee cover sheet CDRH submission form PMA review checklist Certification of compliance with requirements of clinicaltrials.gov data bank Certification: Financial disclosure

25 Submission (2) Technical review documents Device description Safety and effectiveness Environmental analysis Risk management Biocompatibility & sterilization Software review (>10,000 pages) Performance test Packaging, shelf life, and storage testing Human factors and usability testing Manufacturing description (>10,000 pages) Clinical trial data Labeling

26 User fee cover sheet

27 User fee cover sheet - online

28 CDRH Submission form

29 PMA review checklist

30 Certification of compliance with requirements of clinicaltrials.gov data bank

31 Certification: Financial disclosure

32 Technical review: Device description Device generic name Device trade name and model number Company name and corresponding personnel Manufacturing facility Details Shape, color, material, hardware, etc Components (if such exist) User s manual Principle of operation Scientific papers

33 Safety and effectiveness Indication for use Caution for use Warnings Only trained operator may install the device Multiple complexity patient warning Calibration needs Pediatric usage Physical damage to the device

34 Effects to environment Electromagnetic compatibility: IEC Mechanical shock Material hazard Toxicity of the material Pollution during manufacturing

35 Risk management ISO 14971: Medical devices Application of risk management to medical devices IEC : Medical electrical equipment-general requirements for basic safety and essential performance ISO : Statistical interpretation of data

36 Biocompatibility & sterilization Biocompatibility Direct contact with patients Cytotoxicity Irritation Toxicity Genotoxicity Chronic toxicity Sterilization ISO ISO Bioburden recovery method

37 Performance test Test mechanical change during cleaning procedure Mechanical strength test for each part Test assembly of each part Test of mechanical working condition Test of operation due to environment (temperature, humidity, etc) Test of electrical performance Test of performance for system

38 Packaging, shelf life, and storage testing Packaging Sealing Change in shape Contamination Shock, environmental effect Shelf life Storage

39 Human factors and usability testing Human factors: Mater of how to design the product according to each users ability, limit, etc Minimizing error Usability testing: user-interface design validation FDA guidance: Applying human factors and usability engineering to optimize medical device design

40 Manufacturing description (>5,000 pages) GMP ISO x: Biological evaluation of medical devices ISO x: Sterilization of healthcare products ISO x: Packaging for terminally sterilized medical devices ISO x: Cleanrooms and associated controlled environments

41 Clinical trial data Sample size = >200 Ethinicity Test period per person- 7 to 10 days Comparison to existing device Hyperglycemia: 20% error, 80-90% range Hypoglycemia: 20% error, 70-80% range Safety issue: none

42 Labeling ISO 15223: Medical devices symbols to be used with medical device labels, labelling and information to be supplied

43 CGM- software review Will be covered tomorrow

44 Thank you