Efforts to evaluate materials in medical devices to address potential safety questions

Materials used in today’s medical devices vary widely

  • Metal, plastic, silicone, an animal-derived product or some combination
  • Come into contact with tissue or other body parts for extended periods of time
  • Premarket review to determine potential adverse biological response
  • Post-marketing tools to monitor a device’s benefit-risk profile in real-world setting

Further enhance understanding of materials science 

  • Causes for exaggerated response in sensitive individuals
  • Advance development of safer materials
  • Case studies: Breast implants, Metals in devices, Animal materials in devices

CDRH’s OSEL conducting research on new advances in device materials



 New strategies to modernize clinical trials to advance precision medicine, patient protections and more efficient product development

FDA opportunities for agile clinical research enterprise

However, sponsor reluctance to adopt innovative approaches

  • Rigid business model
  • Barriers between real world data and clinical research
  • Limited evidence sharing  across a learning health care system



Focus Areas for Total Budget of $6.1 B

  • Reduce burden of addiction crisis
  • Foster competition by continued implementation of 21st Century Cures Act
  • Empower consumers/patients by promoting patient focused product development
  • Strengthen Science and Evidence-based decision making to enhance safety



New steps to strengthen safety requirements aimed at mitigating risks associated with transmucosal immediate-release fentanyl products

To confront opioid  crisis, Risk Evaluation and Mitigation Strategy (REMS) programs to ensure benefits outweigh risks

  • Opioid Analgesics REMS program covers transmucosal immediate-release fentanyl (TIRF) medicines – 9 products on market
  • Indicated to manage breakthrough pain in adults with cancer who are routinely taking other opioid pain medicines to treat around-the-clock pain

Now modifying TIRF REMS – notifying manufacturers of following required changes

  • Document patient’s opioid tolerance concurrently with each prescription for outpatient use
  • Inpatient pharmacies to develop internal policies and procedures to verify opioid tolerance in hospitalized patients
  • Outpatient use requires evidence of safe use conditions, including concurrent documentation of opioid tolerance
  • New patient registry to monitor for serious adverse events including overdose (both fatal and non-fatal)



 Landmark policy changes to modernize mammography services and improve their quality

Proposed rule would require breast density reporting, enhance the FDA’s ability to enforce mammography facilities’ compliance with standards

  • FDA can directly notify patients and their health care professionals if facility did not meet quality standards
  • Only digital accessory components specifically FDA approved or cleared for mammography can be used
  • Strengthening record-keeping requirements to minimize information loss and improve access to and transfer of patient mammography records



Finalized requirements for tests to detect anthrax-causing bacteria

FDA plays a critical role in protecting our nation from bioterrorism threats such as anthrax

  • Final rule provides review pathway, testing criteria, how to address potential safety risks for lab workers

Regulatory pathway: In vitro diagnostic devices for Bacillus bacteria detection

  • Class II (moderate-risk) with special controls – requires premarket notification 510(k)
  • Provide information on testing criteria and performance evaluations
  • Restriction on distribution to laboratories that follow public health guidelines to address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities, to reduce risks associated specimen handling


Capture.JPGProposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device (SaMD) 

Artificial intelligence and machine learning have the potential to fundamentally transform the delivery of health care

  • Earlier disease detection, more accurate diagnosis, identification of new observations or patterns on human physiology, development of personalized diagnostics and therapeutics
  • Greatest benefits of AI/ML in software is ability to learn from real-world use and experience (training) and improve performance (adaptation)
  • Deliver safe and effective software functionality that improves the quality of care that patients receive.

Use TPLC Model for regulatory framework to balance benefits and risks


  • Quality systems and good ML practices (GMLP)
  • Premarket review for reasonable assurance of safety and effectiveness and continual management of  patient risks throughout lifecycle
  • Risk management approach for development, validation, execution of algorithm changes
  • Increased transparency to users and FDA using postmarket real-world performance reporting for maintaining continued assurance of safety and effectiveness

Framework to allow for modifications to AL/ML algorithms to be made from real-world learning and adaptation

  • Approved technoloigie use  “Locked” algorithms – don’t continually adapt or learn
  • Locked algorithms modified by manufacturer at intervals for “training” of algorithm using new data, followed by manual verification and validation of the updated algorithm.
  • Proposing Predetermined change control plan:  SaMD Pre-Specifications (SPS) and  Algorithm Change Protocol (ACP)



Review and Update of Device Establishment Inspection Processes and Standards


  • Standardized methods of communication during inspection process
  • Practices for investigators and device establishments to facilitate continuity of inspections

Uniformity in investigators’ approaches to inspections inform firms’ inspection preparation

  • Pre-announcement Notice and Communication:  Telephone notification 5 days prior (domestic) or longer (foreign) – inspection is abbreviated, comprehensive, or pre-approval
  • Standard Inspection Timeframe: Generally 3 to 6 continuous business days
  • Communication During Inspections: Regular verbal communications during inspection, discuss all observations to minimize errors and misunderstandings



Enforcement Actions: Breast implant manufacturers, illegal online sales of opioids

Breast Implant Manufacturer

Warning letters for

  • Failure to comply with their requirements to conduct post-approval studies
  • To assess the long-term safety and risks of silicone gel-filled breast implants

Mentor Worldwide LLC and Sientra, Inc.

Illegal online sales of opioids

Warning letters for

  • Illegal marketing potentially dangerous, unapproved and misbranded opioid medications, including tramadol
  •  In addition to health risks, pose other risks to consumers, including credit card fraud, identity theft and computer viruses and

Stem Cell Clinics

Warning letter for

  • Manufacturing unapproved umbilical cord blood products
  • Violation of current good manufacturing practice (CGMP) requirements, including failing to validate processes to prevent bacterial contamination, raising potential significant safety concerns that put patients at risk

Cord for Life

Image credit: FDA