Monday, November 26, 2018

FDA Will Soon Float New 510(k) Guidance; Positions on Drug/Software Pairs and Bayesian Designs

Over the Thanksgiving weekend, FDA Commissioner Dr. Scott Gottlieb tweeted that FDA was about to launch new initiatives to "modernize" the 510(k) process.  

This process is a pillar of the 1976 medical devices law, which generally grandfathered preexisting devices and required review or approval for new devices unless they had pre 1976 "predicates."    An important modernization was the introduction of "de novo 510(k)," a regulatory process that is much faster than a PMA device approval.

The Monday, November 26, 2018, press release from FDA (both Dr. Gottleib and Dr. Shuren of CDRH) is here.   The modernization will focus on shifting manufacturers away from use of "old predicates" and toward use of predicates less than ten years old.  They indicate they will issue a plan for public feedback, meaning either a draft guidance or draft regulation.  No specific date is offered.  FDA notes that some of its "goals" may require "additional guidance from Congress."
  • Although not directly related to 510(k) changes, this article also includes sections further below on:
  • FDA's recent announcements about software directly tied to pharma, and 
  • FDA's recent announcements about Bayesian and other complex trial designs (CITD).  


The FDA seems to be responding to years of criticism of the FDA 510(k) system as too lax, including a burst of new documentaries and books in 2017/2018, e.g. here.   One smoking gun, hitting the public media several years ago, was fatal cancers caused by use of tissue morcellators in minimally invasive uterine fibroid treatments (here; press here on GAO report here).  Another class of issue was manufacturers who viewed existing regulations as endorsing an abilityto get by with 1976-equivalent technology.  (Let's say, as a made-up example, if 1976 glucose meters were plus/minus 20% accurate, and modern ones 5%, you could merely meet the 1976 predicate today).

Links re 510(k) 
  • New Detailed November 26 FDA press release here.  
    • 3400 words.  At 200 wpm, about a 20 minute read.  
      • The current FDA regime uses these "press releases" as substantive and detailed reviews of the agency's plans and next direction, and how it views its own process and goals.  Ignore reading the whole thing, at your peril.
    • Early open access coverage at MedTech Dive, here.  
    • WSJ here.  
    • Genomeweb here.
  • The FDA also issued an 8-page "performance report" on recent achievements and improvements in the 510(k) policy system, here.
  • Last week's November 20 FDA press release on updated device post market surveillance efforts, here.
    • Much of this document describes NEST (see next).
  • November 26, FDA seeks $46M for national health surveillance system NEST, here.
    • FDA home page for NEST, here.
    • NEST involves funding from FDA to the MDIC (Medical Device Innovation Consortium) to set up another body, NEST Coordinating Center or NESTcc.
    • See 8 pilot test cases of NEST projects, here.  
      • The scope would be greatly expanded with $46M instead of several $M.
  • FDA current medical device predicate home page here.
    • Current 2014 PDF guidance on finding and using predicates (42 pp) here.
    • FDA sets the new 510(k) ideas firmly in context of its Medical Device Safety Action Plan, floated in Spring 2018, here.
  • Gottlieb's November 25 "FDA Sunday Tweetorial" on device improvements
  • In separate messaging, such as in December 2017, FDA discussed wanted to ensure that devices could enter the market with "acceptable uncertainty" and not be overly delayed by regulatory review, here.

FDA Sports Metaphor

The November 26 press release gives Gottleib and Shuren a chance to use the (overused?) hockey metaphor "skate to where the puck will be."   "We not only have to skate to where the puck will be, we also need to drive the puck to where it should be."  Both of these risk being obvious; of course you are supposed to skate toward where the puck is going, in order to hit it; and when you do hit it, you are supposed to hit it to where you need it to be next. 


Footnote 01: FDA and Software Directly Related to New Drugs

A year back, in November 2017, I was at a digital health conference where Amgen was discussing its plan to develop drugs closely linked to software packages.   FDA has been pushing forward on that front, too.
  • See a November 19, 2018, press release on FDA proposals to link digital tools with drug approvals, here.
    • See the FDA's corresponding official Request for Public Comment on the proposal (comment open until January 22), here.
    • Trade press on the above, Medtech Dive, here. At RAPS, here.
  • Earlier, May 2018 trade press on FDA and digital devices (Covington), here.
    • Gottleib comments on digital health at Datapalooza April 2018, here.
  • Trade press on digital therapeutics, June 2018, here.  Trade press (RAPS) on FDA and Dhealth and "paradigm shift," April 2018, here.
  • FDA report on how 21st Century Cures impacts FDA medical software policy, here (December 2017, 14 pp).
  • FDA draft guidance on clinical decision support (CDS) software, here (December 2017, 13 pp).
Pre-Certification.  Separately, FDA has been crafting a "pre-certification" system for some types of health related software, with pilot announcements in 2018 and more detail to come by early 2019.   In October 2018, Sen. Warren issued a 12-page letter to FDA requesting more detail about risks of this adventure (PDF from here, trade press here, here.)

Footnote 02:  FDA and Complex Innovative Trial Designs

The 21st Century Cures Act asked FDA to provide guidance and look closely at innovative trial designs (e.g. Bayesian designs).   Some argued that Congress was trying to lower the rigor of FDA design standards, but to my eye, Congress was only asking FDA to "provide guidance" - for example, it could provide guidance it hated Bayesian designs and it would meet the Congressional direction to provide guidance.

In any case, the FDA has latched onto "CITD" - Complex Innovative Trial Designs.  FDA held a full day workshop in March 2018; webpage here.   (See decks, transcripts, video; public comment docket with 12 comments).  See post meeting comments by BIO, PHRMA, Friends of Cancer Research (totalling 44pp); here.

See the FDA homepage for CITD Pilot Program here.

Press release here (August 29, 2018).   Corresponding FDA Fed Reg announcement here.  (83 FR 44274).   Trade press here, here.  RAPS here.

RAPS on September 2018 draft guidances, a pair of them, here.  See #1 Adaptive Designs draft guidance here.  See #2 "Efficient Master Protocol Design to Expedite Development..." draft guidance here.