FDA s 510(k) Working Group

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1 Understing the Premarket Notification (510(k)) Process FDA s 510(k) Working Group Presentation to the Institute of Medicine March 1, 2010 Donna-Bea Tillman, Ph.D. Director, Office of Deice Ealuation U.S. Food Drug Administration

2 How did we get here? The world has changed dramatically since the inception of the 510(k) program in 1976 The 510(k) program has changed along with it: Safe Medical Act of 1990 Indications Use m Class II exemptions Special 510(k) program Ealuation of Automatic Class III Designation (De noo) 2

3 How did we get here? These changes were intended to allow the 510(k) program to keep up with the changing enironment but they hae come with challenges of their own, implementation has not always been perfect. 3

4 FDA s 510(k) Working Group: Charge Take a clear-eyed look at how the 510(k) program is REALLY working Engage staff external constituencies to get their thoughts Prepare a report that will: Describe the current status of the program Identify challenges Make recommendations improement Short term Longer term 4

5 510(k) Working Group: Process Began meeting in September 2009 Established 10 subgroups: Predicates Indications New Technology De Noo Eidence Modifications Stards Bundling Third Party Reiew Postmarket Data 5

6 510(k) Working Group: Process Soliciting input from staff external constituencies: Public Meeting: February 18, 2010 Comment period ends March 19, 2010 CDRH All-Hs Meeting: February 24, 2010 Also collecting staff input through other mechanisms 6

7 510(k) Working Group: Process Current status: Completed identification of challenges Ongoing data collection deelopment of recommendations Beginning analysis of comments from public CDRH All hs meeting Final report due: May 31,

8 Issues Identified by the 510(k) Working Group U.S. Food Drug Administration

9 Issues Related to Predicate Challenge: Manufacturers may lack sufficient inmation to select an appropriate predicate FDA proides limited inmation on our website. 510(k) summaries often lack critical details. FOIA process can be slow only proides redacted inmation. 510(k) statements rely on manufacturer responses, which can be difficult FDA to police. Firm s promotional material may not reflect what was actually cleared inmation submitted to FDA may be inaccurate. FDA s product code process lacks transparency. 9

10 Issues Related to Predicate Challenge: Use of old predicate deices How can the program effectiely efficiently eole if deices from 1976 set the bar comparison? E.g., comparing a manual instrument to one that is micro-processor-controlled How can FDA deal with predicate deices with sub-par permance compared to the other deices in the class? Most tools aailable to FDA to rectify these predicates are labor- time-intensie. 10

11 Issues Related to Predicate Challenge: Use of multiple or split predicates When is it appropriate to use more than one predicate? May make sense some deices (e.g., multiparameter monitors) Citing intended use from one deice the technology from another (split predicate) creates challenges in assessing SE. It is difficult to assess SE when the predicate is from a different deice panel/regulation. E.g., surgical mesh anal fistula repair being used as a predicate orthopedic use 11

12 Issues Related to Indications Use Challenge: Lack of clarity regarding indication use s. intended use Lack of regulatory definitions can create inconsistency (but can also allow flexibility). When is a new indication use a new intended use? Use of lasers to remoe hair was considered a new indication, but not a new intended use, so could be a 510(k). Use of lasers transmyocardial reascularization LASIK were considered a new intended use, so these deices required a PMA. 12

13 Issues Related to Indications Use Challenge: Lack of clarity regarding indication use s. intended use What inmation seres as the basis establishing indications intended use? Determining indications of older submissions prior to the required IFU m can be difficult. 13

14 Issues Related to Indications Use Challenge: General s. specific indications When are tool indications appropriate? When should a specific indication use be found SE to a more general use? Current guidance document identifies seen criteria determining when a specific use falls under the general use includes examples. E.g., endometrial ablation by cryo-ablation found NSE to general use of cryo-ablation in gynecology Inconsistent interpretation of guidance. 14

15 Issues Related to Indications Use Challenge: Difficulty in addressing risks of offlabel use Background: 513(i)(1)(E) of the FDCA addresses curbing of off-label use SE determinations about intended use are based on proposed labeling, unless FDA beliees there is a likelihood that it will be used another purpose, AND that use could cause harm. FDA may require a statement in the labeling which proides inmation about that off-label use (SE with limitations). 15

16 Issues Related to Indications Use Challenge: Difficulty in addressing risks of offlabel use Sponsors often pursue obtain clearance a narrow claim, een when it is obious they re interested in something else. Labeling may be ineffectie in addressing risks of offlabel use. May encourage off-label use Users often do not see the labeling Is it more appropriate FDA to ask more studies? 16

17 Issues Related to New Technology Challenge: Lack of clarity regarding technological differences What factors does FDA need to consider in determining if differences in technology raise a different type of safety/effectieness question? How different is different enough that the deice should no longer be ealuated as a 510(k)? Should the comparison be limited to deices of only the same type? 17

18 Issues Related to the De Noo Process Background: Limited to low- or moderate-risk deices To date has been most successfully applied to certain types of IVDs Challenge: Lack of consistency timeliness De noo process requires that FDA know enough about the deice type to define the risks the Special Controls that may be necessary to mitigate the risks May require issuance of a Special Control guidance Guidance process can be time-consuming 18

19 Issues Related to Leel of Eidence Background: Almost all 510(k)s include some bench or permance data. E.g., biocompatability, electrical safety, mechanical integrity Many also include preclinical testing more directly related to how they will be used. 19

20 Issues Related to Leel of Eidence Challenge: Lack of consistency regarding what leel of eidence is sufficient When is preclinical data enough, when are animal /or clinical data needed? What should the deice be compared to? Limitations of old predicates Role of stard of care May be difficult manufacturer to directly compare to predicate How should serial, incremental modifications be tested? 20

21 Issues Related to Leel of Eidence Challenge: Lack of consistency in the use of clinical data in a 510(k) How does the concept of clinical utility factor into the SE determination? How should FDA interpret clinical studies? How can FDA proide assurance that the deice will perm as intended in real-world use? How should FDA deal with poorly designed studies after the fact? 21

22 Issues Related to Leel of Eidence Challenge: Manufacturing inmation might not be considered during reiew GMPs may not be part of the SE decision unless substantial likelihood that such failure will potentially present a serious risk to human health (Section 513(f)(5) of the FDCA) Limited ability to require a pre-clearance inspection of the deice facility Manufacturing inmation may not be in the 510(k) E.g., detailed engineering inmation about deice design; lot release criteria Majority of recalls are due to manufacturing design control problems 22

23 Issues Related to Deice Modifications Challenge: Incremental design changes deice creep FDA has a guidance on modifications (which is being updated), but it is inconsistently interpreted by firms. Modifications to 510(k) deices are often not submitted. Firms often interpret the regulation which states could affect safety effectieness as does affect. Inmation resides only in firm s internal files, so FDA does not hae the opportunity to reach the same conclusion. 23

24 Issues Related to Deice Modifications Challenge: Incremental design changes deice creep Equialence studies allow not much worse than oer time this can allow deice permance to deteriorate. Incremental changes oer time may collectiely be significant. Current 510(k) may or may not catch up design. Comparatie permance may be based on marketed deice rather than cleared deice. 24

25 Issues Related to Bundling Background: Bundled Submissions E.g., similarly designed dental implants Bundled E.g., bedside monitors with multiple parameters (heart rate, arrhythmia detection, NIBP) 25

26 Issues Related to Bundling Challenge: Bundling creates administratie complications These submissions may be quite complex yet the timeline is the same as a single deice. E.g., submissions bundled across reiew diisions or deice panels Each 510(k) receies a single classification creates challenges in determining how a bundled submission should be classified. It can be difficult to identify bundled products after clearance. 26

27 Issues Related to the Use of Stards Background: Stards are used to streamline the reiew process FDA Industry Agency Resources: FDA Recognized Consensus Stards Database Stards Data Report (Form 3654) 27

28 Issues Related to the Use of Stards Background: Guidance: Use of Stards in Substantial Equialence Determinations onguidance/guidancedocuments/ucm pdf Guidance: Recognition Use of Consensus Stards nce/guidancedocuments/ucm htm Guidance: Frequently Asked Questions on Recognition of Consensus Stards nce/guidancedocuments/ucm htm 28

29 Issues Related to the Use of Stards Challenge: Lack of assessment of conmity to a stard Lack of FDA erification of manufacturers stated conmity to stards Many stards do not contain objectie pass/fail criteria or permance limits 29

30 Issues Related to the Use of Stards Challenge: Manufacturers may lack clarity about appropriate use of stards Inconsistencies in the use of consensus database E.g., not using the appropriate stard or not using the most recent recognized ersion How to appropriately declare conmity to a stard? Use of Form 3654 Needed if a sponsor chooses to use a stard to support an SE determination. Validates the Extent of Recognition followed any deiations Not optional declaration of conmity to stard(s) 30

31 Issues Related to Third Party Reiew Background: Accredited Parties established ~1996 An alternatie route 510(k) reiew Intended to speed the 510(k) reiew process to help FDA manage its large 510(k) workload Approximately 300 applications (8%) are submitted each year 31

32 Issues Related to Third Party Reiew Challenge: Poor-quality third party reiew submissions Most third-party-eligible deices do not hae a deice-specific guidance. Accredited Parties do not hae access to predicate 510(k)s or their reiews. 32

33 Issues Related to Postmarket Data Background: FDA s postmarket controls 510(k) deices are limited. Changes to a cleared deice subject to 510(k) require a new 510(k) or the firm s documentation to the file as to why a 510(k) is not needed. It is difficult to fix/modify or remoe a cleared 510(k). 33

34 Issues Related to Postmarket Data Challenge: FDA has limited authority to mate postmarket sureillance studies after SE determination Een if inmation collected under a postmarket study suggests significant safety effectieness issues, it is difficult to apply that inmation to deice preiously cleared deices. Unlike PMAs, there is no explicit authority FDA to require a condition of approal study clearance of a 510(k) deice. 34

35 Issues Related to Postmarket Data Challenge: FDA has limited authority to rescind 510(k) clearance In the absence of a robust rescission authority, it is difficult FDA to address problematic predicates. Situations that hae led to rescission include: False inmation material to the SE has been discoered. New inmation has shown the deice may hae significant safety effectieness problems. Concerns hae been raised about the domino effect of a rescission the predicates. FDA proposed a 510(k) rescission regulation in

36 Issues Related to Postmarket Data Challenge: Difficulty applying postmarket inmation to future 510(k) reiews How should postmarket inmation be applied to deices under reiew? Difficulty relating general postmarket inmation to specific deices Leel playing field question 36

37 Issues Related to Postmarket Data Challenge: Final printed labeling is not required prior to an SE determination a 510(k) 510(k) holders may change the labeling from the draft submitted in the 510(k). Initial burden is on a 510(k) holder to determine if the change to labeling requires a new 510(k) or not. For exempt deices, FDA does not routinely reiew een draft labeling. 37

38 Issues Related to Postmarket Data Challenge: FDA does not require the purchase, sale, or transfer of ownership of a 510(k) be reported to FDA Difficult FDA to inestigate aderse eents, assign inspections take appropriate encement actions Difficult FDA to erify changes in ownership reported oluntarily Oer 120,000 cleared 510(k)s 38

39 Summary Increasing transparency is essential. Achieing consistency is critical. Deeloping clear definitions, guidance, additional authorities may be required. Utilizing rational application of guiding principles is ital. 39

40 Thank You U.S. Food Drug Administration

Comments of the Patient, Consumer, and Public Health Coalition. Strengthening the Center for Devices and Radiological Health s 510(k) Review Process

March 19, 2010 Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane, Room 1061 Rockville, MD 20852 Comments of the Patient, Consumer, and Public Health Coalition on Strengthening