Remove the Risk- Opioid Disposal Campaign


Remove the Risk- Opioid disposal awareness 

  • In 2017: 191 million opioid prescriptions to almost 60 million patients
  • 90% patients reported not finishing what was prescribed to them
  • Millions of unused prescription opioids in homes if not disposed of properly
  • In 2017: 47,600 people died from an overdose involving opioids

Remove the Risk PR campaign

  •  Targeting women ages 35-64, who are most likely to oversee household health care decisions
  • Information about safe disposal of these medicines.


image: FDA

Drug Authorizations: ZULRESSO for postpartum depression, SUNOSI for daytime sleepiness, MAYZENT for multiple sclerosis, DOVATO for HIV, BALVERSA for metastatic bladder cancer



ZULRESSO (brexanolone) intravenous injection 

Sage Therapeutics

INDICATION: Treatment of postpartum depression (PPD) in adults


  • First drug approved specifically for PPD
  • PPD is a serious condition that can be life-threatening

MECHANISM OF ACTION: Related to positive allosteric modulation of GABA receptors


  • Two multicenter, randomized, double-blind, women (18 to 45 years) with PPD, ZULRESSO vs placebo
  • Primary endpoint: Mean change from baseline in depressive symptoms as measured by HAM-D total score at the end of the infusion
  • Superiority to placebo in improvement of depressive symptoms,  improvement in depression was also observed at the end of the 30-day follow-up period.


  • Boxed Warning: Patients at risk of excessive sedation or sudden loss of consciousness during administration; must be monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring
  • Most common adverse reactions: Sleepiness, dry mouth, loss of consciousness and flushing


  • Priority Review and Breakthrough Therapy designations
  • Approved with a Risk Evaluation and Mitigation Strategy (REMS)- only available through restricted distribution program
  • Recommend scheduling of Zulresso under the Controlled Substances Act (CSA)- DEA scheduling pending
  • Required Pediatric Assessment: In adolescent females, 15 – <18 diagnosed with postpartum depression.


Capture.JPGSUNOSI (solriamfetol) tablets

Jazz Pharmaceuticals

INDICATION: To improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (OSA)

MECHNANISM OF ACTION: Could be mediated through its activity as a dopamine and norepinephrine reuptake inhibitor



  • 12-week, multi-center, randomized, double-blind, placebo-controlled,
    parallel-group study, n=239 patients with narcolepsy
  • Co-primary Endpoints:  Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS). Statistically significant improvements with SUNOSI


  • 12-week multi-center, randomized, double-blind, placebo-controlled study, n=476 patients with OSA
  • Statistically significant improvements with SUNOSI on MWT and ESS


  • Warnings and Precautions: Blood Pressure and Heart Rate Increases, Psychiatric Symptoms
  • Most common adverse reactions: Headache, nausea, decreased appetite, insomnia, anxiety.


  • Recommended scheduling under Controlled Substances Act (CSA)- DEA scheduling pending
  • Postmarketing requirements: Prospective, registry study on maternal, fetal, infant outcomes, additional pregnancy study, lactation study


Capture.JPGMAYZENT (siponimod) tablets 


INIDCATION: Treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.


  •  MS is among the most common causes of neurological disability in young adults and occurs more frequently in women than in men
  •  Can have a profound impact on person’s life
  • Approval provides  a  treatment option

MECHANISM OF ACTION: Sphingosine-1-phosphate (S1P) receptor modulator; binds with high affinity to S1P receptors-  reduces lymphocyte migration into CNS


  • Randomized, double-blind, parallel-group, placebo-controlled, time-to-event study, n=1651 in patients with secondary progressive multiple sclerosis (SPMS), MAYZENT vs placebo
  • Primary endpoint:  Time to three-month confirmed progression in disability
  • Progression of disability statistically significantly lower in Mayzent vs. placebo
  • Decreased number of relapses group with Mayzent


  • Medication Guide:  May increase the risk of infections, may cause macular edema,  may cause transient decreases in heart rate and may cause a decline in lung function and liver fucntion
  • Most common adverse reactions: Headache, high blood pressure and liver function test increases


  • Postmarketing requirements: Clinical Study to assess serious risk of pulmonary toxicity, Prospective pregnancy exposure registry, Pregnancy outcomes study


Capture.JPGDovato (dolutegravir and lamivudine) tablet

ViiV Healthcare

INDICATION: complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults with no antiretroviral treatment history and with no
known substitutions associated with resistance to the individual components of DOVATO


  •  First FDA-approved two-drug, fixed-dose, complete regimen for HIV-infected adults who have never received treatment for HIV
  • Drug-sparing treatment available that uses fewer drugs is beneficial to patients who may have issues taking multiple medications over a long period of time

MECHANISM OF ACTION: Fixed-dose combination of the HIV-1 antiretroviral agents, dolutegravir and lamivudine


  • Two identical, randomized, double-blind, controlled clinical trials, n=1,433 HIV-infected adults with no prior antiretroviral treatment history
  • Primary efficacy endpoint: Proportion of subjects with plasma HIV-1 RNA <50 copies/mL at Week 48
  • Dovato had similar effect of HIV reducion vs drug regimen of dolutegravir, emtricitabine, and tenofovir


  • Boxed Warning: Patients infected with both HIV and hepatitis B should add additional treatment for hepatitis B 
  • Known risk for neural tube defects with dolutegravir- avoid use at the time of conception through first trimester of pregnancy
  • Most common adverse reactions: Headache, diarrhea, nausea, insomnia and fatigue


  • Supportive of DHHS initiative Ending the HIV Epidemic: A Plan for America,
  • Aim to reduce new infections by 75% in the next 5 years and by 90% in the next 10  years, averting more than 250,000 HIV infections in that span


Capture.JPGBALVERSA (erdafitinib) tablets


therascreen FGFR RGQ RT-PCR Kit  


INDICATION: Treatment of adult patients with locally advanced or metastatic
urothelial carcinoma (mUC), that has:

  • susceptible FGFR3 or FGFR2 genetic alterations, and
  • progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

Select patients for therapy based on an FDA-approved companion diagnostic for BALVERSA

ADDRESSING UNMET NEED: First personalized treatment targeting susceptible FGFR genetic alterations for patients with metastatic bladder cancer

MECHANISM OF ACTION: Kinase inhibitor that binds to and inhibits enzymatic activity of FGFR1, FGFR2, FGFR3 and FGFR4; inhibits FGFR phosphorylation and signaling and decreased cell viability in cell lines expressing FGFR genetic alterations


  • Multicenter, open-label, single-arm study, n=87 patients with locally advanced or metastatic bladder cancer, with FGFR3 or FGFR2 genetic alterations, that had progressed following treatment with chemotherapy
  • Major efficacy outcome measures: Objective response rate (ORR), Duration of response (DoR), determined by blinded independent review committee (BIRC) according to RECIST v1.1
  • ORR: 32.2%, with 2.3% having complete response and 30% having partial response
  • DOR: Approximately five-and-a-half months
  • Responses to Balversa were seen in patients who had previously not responded to anti PD-L1/PD-1 therapy


  • Warnings and Precautions: Ocular disorders, Hyperphosphatemia
  • Common side effects: Increased phosphate level, mouth sores, feeling tired, change in kidney function, diarrhea, dry mouth, nails separating from the bed or poor formation of the nail, change in liver function, low salt (sodium) levels, decreased appetite, change in sense of taste, low red blood cells (anemia), dry skin, dry eyes and hair loss. Other side effects include redness, swelling, peeling or tenderness on the hands or feet (hand foot syndrome), constipation, stomach pain, nausea and muscle pain
  • Balversa because it may cause harm to a developing fetus or newborn baby


  • Accelerated Approval, Breakthrough Therapy designation
  • Accelerated approval based on tumor response rate – Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials
  • Accelerated approval requirements: Demonstrating clinical benefit of erdafitinib in patients with locally advanced and metastatic urothelial carcinoma with susceptible FGFR 3 or FGFR 2 genetic alterations


Image credit: Sage, Jazz, Novartis, ViiV, Janssen


Device Authorizations: TRILURON for osteoarthritis, LOADPRO for spine surgery, PLENITY for weight management, LEICA 400 filter for glioma



Fidia Farmaceutici S.p.A.

INDICATION FOR USE: Treatment of pain in osteoarthritis (OA) of the knee in
patients who have failed to respond adequately to conservative nonpharmacologic therapy, and to simple analgesics, e.g., acetaminophen


  • Viscous solution consisting of a high molecular weight (500,000–730,000 daltons) fraction of purified sodium hyaluronate (Hyalectin®) in buffered
    physiological sodium chloride, having a pH of 6.8-7.
  • The sodium hyaluronate is extracted from rooster combs
  •  Hyaluronic acid is a natural complex sugar of the glycosaminoglycan family and is a long-chain polymer containing repeating disaccharide units of Naglucuronate-N-acetylglucosamine
  • Administered by intra-articular injection


  • Retrospective analysis of data prospectively collected from two randomized, controlled trials to determine the effectiveness of TRILURON vs. Hyalgan (control device)
  • Both have identical chemical formulation and differ only in that a lower
    dose is injected (3 weekly injections for TRILURON™ compared to 5 weekly injections of Hyalgan)
  • Primary effectiveness endpoint: Mean change from baseline at 26 weeks in WOMAC Pain scores: TRILURON was non-inferior to Hyalgan
  • Primary evidence of safety of Hyalgan is directly applicable to TRILURON and has already been established


  • Device Procode: MOZ


Capture.JPGLOADPRO™ Intraoperative Rod Strain Sensor

Intellirod Spine, Inc

INDICATION FOR USE: Intraoperative surgical tool that allows surgeons to measure unidirectional rod microstrain on posterior rods in the sagittal plane when performing spine surgery.

Adjunct to surgeon tactile feedback and is not intended to replace a surgeon’s clinical judgment.

Single use, disposable tool to be used in conjunction with X-Spine Systems Fortex Pedicle Screw System for 5.5mm diameter titanium (ASTM F136) or cobalt chrome (ASTM F1537) rod configurations.

GENERIC DEVICE TYPE: Intraoperative orthopedic strain sensor

  • Adjunct tool intended to measure strain on an orthopedic implant in the intraoperative setting only
  • Not intended to provide diagnostic information or influence clinical decision-making.


  • Prolonged operative time due to device error or use error: Usability Testing, Non-clinical Performance Testing, Software verification, validation, and hazard analysis, Labeling 
  • Electrical shock or device failure due to interference from other devices: Electromagnetic compatibility testing, Electrical safety testing 
  • Infection: Sterilization validation, Reprocessing validation, Shelf life testing
  • Adverse tissue reaction: Biocompatibility evaluation


  • Regulation Number: 21 CFR 888.3090
  • Regulation Name: Intraoperative orthopedic strain sensor
  • Regulatory Class: Class II
  • Product Code: QFP



PLENITY device for weight management and/or weight loss

Gelesis, Inc.

INDICATION FOR USE: To aid in weight management in overweight and obese adults with a Body Mass Index (BMI) of 25 – 40 kg/m2, when used in conjunction with diet and exercise

GENERIC DEVICE TYPE: Ingested, transient, space occupying device for weight management and/or weight loss

  • Ingested material that transiently occupies space in the stomach
  • Device passes from the body via the natural gastrointestinal tract


  • Device related gastrointestinal adverse events, including:  Obstruction,  Dilation,  Diarrhea, Constipation, Dehydration: Clinical performance testing, Non-clinical performance testing, Labeling, Shelf life testing
  • Weight gain: Clinical performance testing, Labeling 
  • Interaction with medication: Clinical performance testing, Non-clinical performance testing, Labeling 
  • Adverse tissue reaction: Biocompatibility evaluation
  • Infection: Non-clinical performance testing. Shelf life testing


  • Regulation Number: 21 CFR 876.5982
  • Regulation Name: Ingested, transient, space occupying device for weight management and/or weight loss
  • Regulatory Class: Class II
  • Product Code: QFQ



Leica FL400 surgical microscope accessory filter


INDICATION FOR USE: Surgical microscope accessory filter set for viewing fluorescence of fluorophores comprising an excitation filter for blue spectral range 380 nm – 430 nm and an  observation filter comprising the long-wave blue, green, yellow and red spectrum in the spectral band greater than 444 nm.

Surgical microscope accessory used in fluorescent visualization of suspected grade III or IV gliomas during neurosurgery.

GENERIC DEVICE TYPE: Diagnostic neurosurgical microscope filter

  • Device intended for use during neurosurgery to visualize fluorescence and enhance visualization of tissue associated with a specific disease or condition


  •  False positive: visualization of fluorescence when in fact no target fluorophore is present: Non-clinical performance testing and Labeling
  • False negative: no visualization of fluorescence when in fact the target fluorophore is present:  Non-clinical performance testing and Labeling

REG PATHWAY: De Novo request for Accessory

  • Microscope cleared via 510(k) pathway
  • De novo request for filter as ‘accessory’
  • Regulation Number: 21 CFR 882.4950
  • Regulation Name: Diagnostic neurosurgical microscope filter
  • Regulatory Class: Class II
  • Product Code: QFX


Image credits: Fidia, Intellirod Spine, Gelesis, Leica

Enforcement Actions: INOVA Genomics unapproved tests, Duodenoscope contamination, Unapproved Concussion Apps, Reused/Unauthorized Test Strips



Inova Genomics Laboratory Warning Letter

Marketing in the US without marketing clearances or approvals, in violation of the Federal Food, Drug, and Cosmetic Act
  • MediMap ADHD, MediMap Mind, MediMap Plus, MediMap Heart, MediMap Baby
  • Being marketed as genetic tests for predicting medication response, reducing negative side effects,  discovering the right drug and right dose for a patient…
  • MediMap tests are devices based on intended uses
  • Clinical validity  not established for their intended uses
  • Pose significant public health concerns- inaccurate test results could impact the decision-making of healthcare providers and patients, seriously detrimental to patient health

Not considered as a Lab Developed Test (LDT) that is exempt from FDA’s premarket review or labeling requirements

WARNING: Inova Genomics


High Duodenoscope Contamination Rate

  • Postmarket surveillance studies by  all three manufacturers (Fujifilm Medical Systems USA, Inc, Olympus Medical Systems Corporation, Pentax of America)
  • Evaluate % duodenoscopes which remain contaminated after use of labeled reprocessing instructions
  • Preliminary results (3/2019) indicate higher than expected levels (0.4%)  of contamination
  • Root cause analyses are currently underway; importance of strictly adhering to manufacturer’s reprocessing and maintenance instructions

SAFETY: Duodenoscope Reprocessing


Unapproved or uncleared Apps for concussion

Potential serious risks associated with use of unapproved or uncleared Apps 

  • Marketed to coaches or parents for use during sporting events
  • Could result in an incorrect diagnosis, potentially leading to person with serious head injury returning to their normal activities instead of getting medical care
  • FDA became aware of violative products being marketed to consumers – asked to  remove such claims
  • Will continue to monitor marketplace for devices making unsubstantiated claims and will take further action if necessary
  • Limited number of medical devices that have been FDA cleared or approved to aid in the diagnosis, treatment, or management of concussion – all require evaluation by health care professional

WARNING: Concussion Assessment


Previously Owned Test Strips or Test Strips Not Authorized for US Sale

Marketing of pre-owned test strips or test strips not authorized for sale in the U.S.

  • Sold through online marketplaces- Amazon, eBay, Craigslist, or directly from seller
  • Pre-Owned Strips :  Unsafe, poor storage, tampering, infection risk from previous owner’s blood – Inaccurate test results
  • Test strips not authorized for US sale: Suboptimal quality, inaccurate results

WARNING: Glucose test strips

Image credit: FDA


News & Views: Acting Commissioner, FDA and CBP collaboration, Cannabis-derived product regulation, E-cigarette addiction treatment, Risk-Based Monitoring, Medical Counter Measures, Class I Accessories, Office of Minority Health and Health Equity

Transition of FDA Leadership: Dr. Ned Sharpless as Acting Commissioner

Farewell to Commissioner Gottlieb







FDA and CBP bolster collaboration to protect public health and safety

FDA and CBP agreement to maximize inspection and detection capabilities

  • Prevent illegal and harmful products entering International Mail Facilities and Ports of Entry
  • Sharing of FDA’s advanced screening technology to identify trends in future entries
  • Shared space and increased scientific presence at high-risk/high-volume facilities



Continued evaluation of potential regulatory pathways for cannabis-containing and cannabis-derived products

Products containing cannabis or cannabis derivatives marketed as human drugs, dietary supplements, conventional foods, animal foods/drugs, cosmetics

  • Public hearing on May 31 to share experiences and challenges and product safety
  • Formation of high-level internal agency working group on potential pathways for dietary supplements to be lawfully marketed
  • Webpage on FDA’s requirements for these products
  • Issuance of multiple warning letters to companies marketing CBD products with  unfounded claims aimed at vulnerable populations



Treatment strategies for nicotine addiction and teen use of e-cigarettes

To address troubling epidemic of youth e-cigarette use

  • Youth Tobacco Prevention Plan to ensure no tobacco products marketed to kids
  • Enforcement actions on illegal sales
  • Public education campaigns to warn youth
  • Advanced new policies aimed at preventing youth access to flavored tobacco products, including e-cigarettes and cigars
  • Workshop to examine science and treatment strategies for youth tobacco cessation


Capture.JPGA Risk-Based Approach to Monitoring of Clinical Investigations

Scope: identifying critical data and processes necessary for human subject protection,investigation integrity, risk assessment, specific monitoring plan

  • Tailor monitoring plans to needs of investigation
  • Factors to consider in developing monitoring plan
  • Examples of monitoring methods and techniques
  • Risk-based monitoring important tool to identify and address issue

Monitoring Approach: include information regarding identified risks and how monitoring methods will address those risks

Monitoring Plan Content: A detailed list

Follow-Up and Communication of Monitoring Results: Significant issues identified through monitoring with appropriate Corrective and Preventive Actions



Medical CounterMeasures (MCMs) update

FDA responsible for safety and effectiveness of MCMs—drugs, therapeutic biologics,vaccines, devices, such as diagnostic tests

  • Smallpox preparedness: TPOXX for treatment of smallpox
  • Chemical nerve agent preparedness: Atropine autoinjector for treatment of poisoning by susceptible organophosphorous nerve agents and Seizalam (midazolam intramuscular injection) for the treatment of status epilepticus
  • Radiological/nuclear emergency preparedness: New indication for Leukine (sargramostim) to increase survival in acute exposure to radiation
  • Viral encephalitis preparedness: IXIARO Japanese Encephalitis Virus Vaccine
  • Zika protection: COBAS Zika to screen Zika virus in blood donations
  • Pandemic influenza preparedness: FLUARIX Influenza Virus Vaccine



Finalized List of Accessories Suitable for Class I

For  accessory to be eligible for class I distinct from another device if the accessory

  • is not for use in supporting or sustaining human life
  • does not represent potential unreasonable risk of illness or injury
  • general controls sufficient for reasonable assurance of safety and effectiveness
§ 876.1080 Gastroenterology-urology accessories to a biopsy instrument
§ 876.3500 Penile implant surgical accessories
§ 876.4630 Ureteral stent accessories
§ 876.5012 Biliary stent, drain, and dilator accessories
§ 876.5100 Suprapubic catheter accessories
§ 876.5290 Implanted mechanical/hydraulic urinary continence device surgical accessories
§ 878.5080 Air-handling apparatus accessory
§ 886.4355 Corneal inlay inserter handle


CaptureFDA OMH has a new name: FDA Office of Minority Health and Health Equity (OMHHE)

Reorganization reflects commitment to modernizing structure to:

  • Advance mission to protect and promote public health
  • Meet challenges of rapid innovation across industries regulated by FDA
  • Better captures breadth of portfolio and continue to address needs of racial and ethnic minority populations and underserved communities

New organization chart

Image credit: FDA


Fact or Fiction: Smoking Cessation and Medications



Fact or Fiction: What to Know About Smoking Cessation and Medications

The best way to quit is “cold turkey.” FICTION!

All smoking cessation medications are the same. FICTION!

E-cigarettes are not an approved method to help people quit smoking. FACT!

Nicotine is not the primary cause of cancer from most tobacco products. FACT!

It is dangerous to use more than one nicotine replacement therapy product at the same time. FICTION!

Nicotine replacement therapy gum is different than regular gum. FACT!

Nicotine replacement therapy can be used only for the duration listed on the label. FICTION!

If you’ve tried nicotine replacement therapy in the past and it didn’t work, there is still reason to try it again. FACT!

Image credit: FDA




News & Views: Novel device materials, Modernize clinical trials, 2020 focus areas, New opioid REMS, Modernize mammography, Anthrax diagnostic reg pathway, AI/ML reg framework, Device inspections, Enforcement Actions



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