News & Views: FDA opens, CDRH record-setting year, New Drug Class for Migraines

FDA Opens


Capture.JPGCapture.JPGCDRH-Record Year for Device Innovation

Success in advancing device innovation and approval/clearance novel, safe and effective technologies

  • Approval of 106 novel devices, surpassing the 40-year record we set in 2017 of 99
  • Granted 112 Breakthrough Device Designation requests;  9 approved/cleared

Examples of innovative products

  • Automated insulin dosing system – including for those as young as age 7
  • World’s smallest heart valve for newborns
  • First blood test in the world to evaluate mild traumatic brain injury
  • First mobile medical app to help treat substance abuse disorders\
  • Artificial Intelligence to detect diabetic retinopathy in adults
  • Artificial Intelligence to detect wrist fractures
  • First artificial iris


captureNew Drug Class Employs Novel Mechanism for Migraine Treatment and Prevention

Recently approved drug class targeting  calcitonin gene-related peptide (CGRP) – elevated in blood serum during migraine attacks

  • New migraine drugs block effects of CGRP
  • Specialized monoclonal antibodies cloned subclasses of immunoglobulin G (IgG)
  • Designed to have low potential to interact with other drugs
  • Metabolized differently with fewer adverse reactions
  • Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), Emgality (galcanezumab-gnlm)


Image credit: FDA



Framework for Safety and Performance Based Pathway


Framework for the Safety and Performance Based Pathway

Modernized pathway to facilitate 510(k) Submissions

Safety and Performance Based Pathway when: 

  • New device has indications for use and technological characteristics that do not raise different questions of safety and effectiveness than identified predicate
  • Predicate is within  scope of list of eligible device types
  • Performance criteria align with performance of predicate
  • New device meets all the FDA-identified performance criteria.


  • Use pathway instead of conducting direct comparison testing to predicate despite technological differences
  • Will still need to identify a predicate for certain aspects of substantial equivalence, when appropriate.



New & Views: Shutdown snapshots, Gene Therapy policies, Sentinel safety surveillance, 510(k) modernization, Accelerated Approval labeling

Shutdown Snapshots 





Capture.JPGNew policies to advance development of safe and effective cell and gene therapies

Surge of cell and gene therapy products reflecting significant scientific advancement 

  • Anticipate >200 INDs /year by 2020
  • Anticipate approving 10 1 20 cell and gene therapy products/year  by 2025

New policies to advance development and approval

  1. Expediting programs including regenerative medicine advanced therapy (RMAT) designation and accelerated approval
  2. Series of clinical guidance documents on different areas of development including neurodegenerative diseases
  3. Efficient pathways for regulatory compliance particularly to assist small sponsors, including academic investigators


Capture.JPGThe Future of FDA’s Electronic Safety Surveillance

Sentinel is integral part of FDA’s safety monitoring efforts

  • Influential in range of outcomes including label changes, Advisory Committees meetings, safety evidence
  • Widespread use of real world evidence (RWE) to increase product development  efficiency and lower cost
  • Pursuing ways to better incorporate information from electronic health records (EHRs) into pre- and post-market surveillance

Five-year strategy

  • Enhance and expand the Sentinel System’s foundation, including data, infrastructure, operations and technology;
  • Augment Sentinel’s safety analysis capabilities using advances in data science and signal detection;
  • Use Sentinel System to accelerate access to and broaden the use of real world data for real world evidence;
  • Broaden the Sentinel System’s ecosystem of stakeholders to pursue the vision of a national resource; and
  • Disseminate knowledge and advance regulatory science to encourage innovation and meet the agency’s scientific needs.


Capture.JPGSteps to strengthen its 510(k) pathway by promoting the use of robust performance criteria and modern predicate devices

Safety and Performance Based Pathway

  • Expands approach previously applied through Abbreviated 510(k) Program, based on conformity to FDA-recognized consensus standards
  • Show new device meets FDA-identified performance criteria reflecting current technological principles and the safety and performance of modern predicate devices
  • May request and review underlying data and testing methodologies for substantially equivalent assessment

Promoting use of more modern predicate devices

  • Make public a list of devices or manufacturers who make technologies that rely on predicates that have been on the market for more than a certain number of years (e.g., 10 years)
  • Consider using other criteria to inform our point of reference?
  • Promote use of more modern predicates
  • New authority, such as making at least some older devices ineligible as predicates



Labeling for drugs approved under accelerated approval, reflecting the more frequent use of this pathway for drugs used in certain clinical settings

Focus on indications for drugs approved via accelerated approval based on surrogate endpoint or clinical endpoint other than survival or irreversible morbidity

Example: This indication is approved under accelerated approval based on {state effect on surrogate endpoint or intermediate clinical endpoint that supported the accelerated approval} [see Clinical Studies (14.X)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).


  • Limitations of Usefulness and Clinical Benefit : Uncertainty, Continued Approval
  • When Clinical Benefit Has Been Verified
  • Withdrawal of an Accelerated Approved Indication: Lack of Evidence Concerning the Withdrawn Indication, Safety Information Concerning the Withdrawn Indication


Image credit: FDA

Novel Device Market Authorizations: MIRIS Human Milk Analyzer, SEM Scanner for pressure ulcer, EyeBOX for concussion, ENLIGHT 1810 for mechanical ventilation


MIRIS Human Milk Analyzer

Miris AB

INDICATION FOR USE: Quantitatively measures the concentration of fat, carbohydrate, and protein in human milk. The Miris HMA also provides calculated values for total solids and energy. These measurements, in conjunction with other clinical assessments, may be used to aid in the nutritional management of newborns, including preterm, and infants. This device is intended for use in healthcare by trained healthcare personnel at clinical laboratories.


  • Some infants — including those who may be born preterm or have certain health conditions — may need additional nutrients in order to support their optimal growth
  • Doctors have access to test to analyze nutrients in breast milk to aid parents and healthcare providers

DESCRIPTION: Breast Milk Macronutrients Test System

  • Intended to quantitatively measure fat, protein, and total carbohydrate content in human breast milk. These measurements, in conjunction with other clinical assessments, may be used to aid in the nutritional management of infants


  • N= 112 samples of human milk; comparison of machine vs expected values
  • Device effective at determining levels of protein, fat and carbohydrate in the milk
  • However, certain medications taken by nursing mother could interfere with test’s ability


  • Incorrect test results: General controls and special controls 
  • Incorrect action based on test results: General controls and special controls 


  • Regulation Number: 21 CFR 862.1493 
  • Regulation Name: Breast milk macronutrients test system
  • Regulatory Class: Class II 
  • Product Code: QEI



SEM Scanner (Model 200) for Pressure Ulcers

Bruin Biometrics

INDICATION FOR USE: Intended to be used by healthcare professionals as an adjunct to standard of care when assessing the heels and sacrum of patients who are at increased risk for pressure ulcers

DESCRIPTION: Pressure ulcer management tool

  • Prescription device intended for patients at risk of developing pressure ulcers. The device provides output that supports a user’s decision to increase intervention. The device is an adjunct tool for pressure ulcer management that is not intended for detection or diagnostic purposes.


  • Class I (general) controls provide reasonable assurance of safety and effectiveness 
  • Identified risks to health are adverse tissue reaction, transmission of infection between patients, electromagnetic interference with patient monitoring equipment, electrical shock


  • Regulation Number: 21 CFR 876.2100
  • Regulation Name: Pressure ulcer management tool 
  • Regulatory Class: Class I 
  • Product Code: QEF





INDICATION FOR USE: Intended to measure and analyze eye movements as an aid in the diagnosis of concussion within one week of head injury in patients 5 through 67 years of age in conjunction with a standard neurological assessment of concussion.
A negative EyeBOX classification may correspond to eye movement that is consistent with a lack of concussion.
A positive EyeBOX classification corresponds to eye movement that may be present in both patients with or without concussion.

DESCRIPTION: Traumatic brain injury eye movement assessment aid

  • Prescription device that uses a patient’s tracked eye movements to provide an interpretation of the functional condition of the patient’s brain. This device is an assessment aid that is not intended for standalone detection or diagnostic purposes.


  • Incorrect or misinterpreted results, including: False positive (brain injury when in fact none is present), False negative (no brain injury when in fact brain injury is present): Clinical performance testing, Software verification, validation, and hazard analysis; Labeling
  • Interference with other devices: Electromagnetic compatibility (EMC) testing
    Software verification, validation, and hazard analysis 
  • Electrical shock or burn: Electrical safety testing, Software verification, validation, and hazard analysis 
  • Adverse tissue reaction: Biocompatibility evaluation
  • Eye hazard or injury: Light hazard assessment


  • Regulation Number: 21 CFR 882.1455 
  • Regulation Name: Traumatic brain injury eye movement assessment aid 
  • Regulatory Class: Class II 
  • Product Code: QEA



ENLIGHT 1810 Ventilatory Device


INDICATION FOR USE:  Non-invasive, non-radiation medical device that provides information of local impedance variation within a cross-section of a patient’s thorax. This information is presented to the clinician user as an adjunctive tool to other clinical information in order to support the user’s assessment of variations in regional air content within a cross section of a patient’s lungs.
It is intended for mechanically ventilated adult patients in a hospital setting, whose thorax perimeter is within the range of 78-122 cm.

DESCRIPTION: Ventilatory electrical impedance tomograph

  • Prescription non-invasive, non-radiological ventilatory device that provides an assessment of local impedance variation within a cross-section of a patient’s thorax


  • Adverse tissue reaction: Biocompatibility evaluation 
  • Electromagnetic interference with other devices: Electromagnetic compatibility testing, Infection Reprocessing validation, Labeling 
  • Inaccurate images due to either device hardware or software failure/malfunction: Software verification, validation, hazard analysis, Non-clinical performance testing, Labeling 
  • Electrical shock injury or thermal injury: Electrical, thermal, and mechanical safety testing; Software verification, validation and hazard analysis; Non-clinical performance testing; Labeling


  • 21 CFR 868.1505 
  • Regulation Name: Ventilatory electrical impedance tomograph 
  • Regulatory Class: Class II 
  • Product Code: QEB


Image credits: Miris, Bruin Biometrics, Oculogica, Timpel

News & Views: 2019 Shutdown and Funding Lapse, Breakthrough Devices, Safer Technologies Program, Software Precertification Program Model v1.0, Sentinel System Roadmap


FDA 2019 Lapse in Funding Information

Agency operations continue to the extent permitted by law necessary to address imminent threats

  •  Handle and respond to emergencies
  • Mission critical surveillance for significant safety concerns with medical devices and other medical products

Activities funded by carryover user fee funds

  • NO acceptance of regulatory submissions for FY 2019 that require a fee payment and that are submitted during the lapse period

READ  ………………………………………………………………………………

Breakthrough Devices Program


  • Provide timely access to patients and health care providers by speeding up development, assessment, and review (PMA, 510(k), De Novo)
  • Replaces Expedited Access Pathway and Priority Review for medical devices


  • Efficient FDA interaction during premarket review phase
  • Prioritized review of submission

READ ………………………………………………………………………………


Safer Technologies Program (STeP)

As part of Medical Device Safety Action Plan, STeP is for devices that treat less serious conditions and innovate on safety 

  • For devices that do not otherwise meet ‘breakthrough device’ criteria
  • Has the potential to be significantly safer than currently available alternative treatments or diagnostics
  • Additional details to be provided later

Substantial safety innovations could include

  • Reduce occurrence of serious adverse event or other safety issue
  • Address known device failure mode or common user error
  • Provide for significant safety advantages for users

READ ………………………………………………………………………………

Capture.JPGDigital Health Software Precertification (Pre-Cert) Program: v1.0 Working Model


  • Streamlined and efficient regulatory oversight of software-based medical devices
  • Manufacturers who have demonstrated robust culture of quality and organizational excellence
  • Manufacturers who are committed to monitoring real-world post-marketing performance

Proposed key components 

  • Excellence Appraisal: Five excellence principles of patient safety, product quality, clinical responsibility, cybersecurity responsibility, and proactive culture
  • Review: De Novo classification process with review corresponding to excellence principles
  • Streamlined Review: Interactive review of  software product with special controls and TPLC approach
  • Real-world Performance: Type of information about how software product is performing with patients and emerging risks


READ  ………………………………………………………………………………


Sentinel System – Five-Year Strategy 2019-2023

Sentinel System

  • Core feature of medical product post-market safety surveillance armamentarium
  • Proactively monitors product safety, methodological innovation, real-world evidence
  • Roadmap to focus on innovations emerging from new data science disciplines (NLP, ML), , expand access and use of EHRs

Five Strategic Aims

  • Enhance and expand foundation, including data, infrastructure, operations and technology
  • Augment safety analysis capabilities using advanced data science, signal detection
  • Accelerate access to and broaden use of real-world data  for real-world evidence
  • Broaden stakeholder ecosystem
  • Disseminate knowledge and advance regulatory science

READ ………………………………………………………………………………

Image credits: FDA

2018 New Drug Approvals


2018 New Drug Approvals

  • Rare Diseases: 34 novel approvals including treatments for of rickets, Fabry disease, phenylketonuria
  • Infectious Diseases: Notables include treatments for smallpox, malaria, HIV-1, nontuberculous mycobacterial lung disease
  • Neurological Disorders: Notables include treatment for seizures in Lennox-Gastaut syndrome and Dravet syndrome, migraine, polyneuropathy in hereditary transthyretin-mediated amyloidosis, multiple sclerosis in children
  • Heart, Lung, and Circulatory Diseases: Notable include treatment of hereditary angioedema
  • Women’s Health:  First new treatment for endometriosis pain,  first vaginal ring contraceptive for use for an entire year
  • Cancer and Blood Disorders: New advances for breast cancer, prostate cancer, lung cancer, melanoma, cancer in pancreas or gastrointestinal tract, first treatment  for pheochromocytoma or paraganglioma, new cancer therapy to treat any tumor with specific genetic marker, acute myeloid leukemia, classical Hodgkin lymphoma, acute lymphoblastic leukemia, mycosis fungoides or Sézary syndrome,  thrombocytopenia
  • Other: Non-opioid drug product  for opioid withdrawal symptoms, non-opioid nerve block therapy,  ulcerative colitis, neurotrophic keratitis, seven new biosimilars