News and Views: Orphan products grants, Cybersecurity, Opioid disposal toolkit, Opioid Use Disorder guidance, Breast implants patient labeling, Flu vaccine

Funding to advance medical products for the treatment of rare diseases

 Orphan Drugs are for rare diseases/disorders that affect fewer than 200,000 people in the US

Six new clinical trial research grants to principal investigators from academia and industry totaling over $16 million over the next four years 

  • Stargardt disease
  • Prevention of graft versus host disease
  • Cystic fibrosis patients colonized with nontuberculosis mycobacterium
  • CD4 positive T cell neoplasms
  • Pancreatic cancer
  • Peripheral T-cell lymphoma


FDA and Cybersecurity

Medical devices are increasingly connected to the Internet, hospital networks, and other medical devices to improve health care

  • Increase the risk of potential cybersecurity threats and impact device safety and effectiveness
  • Reducing cybersecurity risks is important but challenging

Fact Sheet on FDA’s role in medical device cybersecurity

  • FDA works closely with several federal government agencies including the U.S. Department of Homeland Security
  • Manufacturers must address pre-market and post-market cybersecurity risks; make updates to strengthen cybersecurity
  • Manufacturer is responsible for software validation to address cybersecurity vulnerabilities, conduct pre-market testing including the use of OTS software

Fact sheet

Safe Opioid Disposal ‘Remove the Risk’ Outreach Toolkit

Remove the Risk raises awareness of the serious dangers of keeping unused opioid pain medicines in the home and provides information about safe disposal of these medicines

  • Free toolkit materials—public service announcements (PSAs), social media images and posts, fact sheets
  • Designed to help groups speak with others about safe opioid disposal

Remove the Risk

Guidance to Encourage Development of Novel Medicines to Treat Opioid Use Disorder (OUD)

Guidance addresses acceptable clinical endpoints for demonstrating effectiveness to treat OUD and to predict a sustained clinical benefit

  • Reductions in adverse outcomes related to OUD (mortality, emergency medical interventions, Hep C infections)
  • Change in disease status using OUD diagnostic criteria
  • Change in drug use pattern
  • Patient Reported Outcomes (e.g., improvement in sleep or mood)
  • Other outcome measures (e.g. ability to resume work, school, or other productive activity)


Breast Implants Labeling Recommendations to Improve Patient Communication

FDA guidances to help ensure that a patient receives and understands the benefits and risks of breast implants

  • Labeling for saline/silicone breast implants for breast augmentation or breast reconstruction
  • Important for patients to have benefit and risk information for a balanced discussion with their physicians
  • Includes: Boxed Warning, Patient Decision checklist, Rupture Screening recommendation, Material/Device description, Patient Device card


FDA approved Flu vaccines provide important benefits such as preventing illnesses, hospitalizations and deaths

  • Likely that flu viruses and COVID-19 will circulate together this fall and winter; flu shot will not prevent COVID-19 but help to keep you healthy and preserve health care resources for COVID-19
  • Annual vaccination to prevent flu is the best way to reduce the risk of getting the flu and spreading it to others
  • Annual shots are needed because flu viruses can change from year to year, so the vaccine is updated; FDA, WHO, CDC, and public health experts collaborate to identify likely strains
  • Typically, children and older people are most at risk of getting sick with influenza
  • FDA ensures flu vaccine is safe, effective, and of high quality


Image credits: FDA, DHS

COVID-19: CDRH response to date, Patient outreach toolkit, Laboratory safety, Vaccine EUA guidance, Medical countermeasures R&D

Center for Devices and Radiological Health’s (CDRH) Response to Coronavirus (COVID-19)

Timeline: January 1 – September 18, 2020

  • Regulatory Flexibility: EUA templates, guidance documents, policies
  • Emergency Use Authorizations: 10x medical devices the number authorized pre-2020, tests
  • Shortage Mitigation Activities: Outreach to 1,000+ manufacturing sites across 12 countries
  • Public Health Service Corps Deployment: 58 CDRH Commissioned Corps officers
  • Engagement with Stakeholders: Emails, phine queries, webinars, townhalls

Patient Outreach Toolkit

Useful COVID-19 resources for healthcare professionals to share with patients

Fraudulent Products Factsheet
(English / Español – PDF, 1.2MB)

FDA Response to COVID-19: What You Need to Know Infographic
(English / Español – PDF, 4.4MB)

Approved COVID-19 Tweets
(English / Español – PDF, 1.6MB)

A Culture of Responsibility: Laboratory Safety at the FDA

In observance on NIH’s Biosafety & Biosecurity Month, FDA is implementing the folloiwng in its labs

  • Proper use of PPE (masks, face shields, gloves, gowns, shoe covers)
  • Engineering controls (biosafety cabinets, secure rooms)
  • Administrative controls (risk assessment, pre-work approval, medical surveillance, respiratory protection programs)
  • Best practices for decontaminating surfaces and proper procedures for packing and transporting any hazardous biomaterials, including SARS-CoV-2


Industry Guidance: Emergency Use Authorization for
Vaccines to Prevent COVID-19

Data and information needed for Emergency Use Authorization (EUA) for an investigational COVID-19 vaccine that could be potentially administered to millions of individuals

  • Chemistry, manufacturing, and controls information (CMC); nonclinical data and information; and clinical data and information, as well as administrative and regulatory information

Safety and Effectiveness Information for evaluation of benefit-risk profile

  • Bioassays for assessment of clinical endpoints
  • Supportive nonclinical studies e.g., characterization of markers associated with enhanced disease, biodistribution, shedding, and attenuation)
  • Clinical
    a. Prespecified success criteria for primary efficacy endpoint (previous guidance), placebo controlled efficacy trial of at least 50%
    b. All safety with focus on serious adverse events, adverse events of special interest, and cases of severe COVID-19 among study subject
    c. Data from Phase 3 studies should include a median follow-up duration of at least two months after completion of the full vaccination regimen
  • In addition
    a. Local and systemic solicited adverse reactions for reactogenicity
    b. All safety data from database lack, n> 3,000
    c. Sufficient cases of severe COVID-19 among study subjects
    d. Sufficient cases of individuals with prior SARS-CoV-2 infection


Cellular signaling and immune correlates for SARS-CoV-2 infection

Research award to Stanford University to help inform the development and FDA review of COVID-19 medical countermeasures

  • Explain host factors contributing to coronavirus immune responses to more rapidly predict patient outcomes
  • Innovative in-depth analysis of existing tissue samples from previous clinical and nonclinical studies
  • Profile circulating immune signatures of coronavirus infection, pathology, tissue imaging, tissue viral reservoirs, how different systems in the body are affected


Image credit: FDA, Stanford University

News & Views : New drug importation pathway, Digital Health center of excellence, ‘Intended Use’ clarification, Illegal opioid websites, Youth E-cig use trend, Collaborative communities, Promoting patient safety, Cannabis Drug Master Files

Importation of Certain FDA Approved Human Prescription Drugs, Including Biological Products, and Combination Products

Potential pathway for manufacturers to commercialize an FDA-approved drug originally intended to be marketed in a foreign country and authorized for sale in that foreign country

  • The final rule allows FDA-authorized programs to import certain prescription drugs from Canada
  • Under specific conditions to ensure no additional risk to the public’s health and safety
  • Could achieve significant reduction in the cost of covered products to the American consumer
  • Guidance provides procedures to interested manufacturers


New Digital Health Center of Excellence

Digital Health Center of Excellence for the advancement of digital health technology

  • Mobile health devices, Software as a Medical Device (SaMD), Wearables medical products
  • Centralized expertise and resource for digital health technologies and policy for digital health innovators, public, FDA staff
  • Goal: Advance health care by fostering responsible and high-quality digital health innovation
  • Objectives: Connect and build partnerships, Share knowledge,  Innovate regulatory approaches 
  • Bakul Patel appointed Director


Types of Evidence Relevant to Determining the “Intended Use” of FDA-Regulated Products

To clarify the regulatory language describing the types of evidence relevant to determining a product’s intended uses

  • Any relevant source of evidence may be considered
  • However, an unapproved use, standing alone, is not sufficient
  • Examples provided in Final Rule


FDA Warns Website Operators Illegally Selling Opioids to Consumers

Warning letters to 17 website operators for illegally selling unapproved and misbranded opioids online in violation of the Federal Food, Drug, and Cosmetic Act

  • Sale without prescription
  • Lack adequate directions for use
  • Put consumers at risk of addiction, abuse and misuse
  • Can lead to overdose and death

Warning letters issued to:,,,,,,,,,,,,,, Thomas Meds,,


Encouraging Decline in Overall Youth E-Cigarette Use, However, concerning Uptick in Use of Disposable Products

New data from the 2020 National Youth Tobacco Survey (NYTS)

  • 1.8 million fewer U.S. youth currently using e-cigarettes compared to 2019
  • However, 3.6 million U.S. youth still use e-cigarettes – a public health crisis
  • Alarming uptick in use of disposable e-cigarettes (e.g. ENDS) by youth – 26.5% of high school and 15.2% of middle school students  
  • All new and existing tobacco products need to submit premarket application for FDA review for marketing authorization – DEADLINE 9/9
  • FDA will take action if products targeted to kids; warnings letters already already issued to some


Collaborative Communities: FDA Participates in 3 New Communities

Collaborative community is a private- and public-sector collaboration which can include the FDA

  • CDRH works together on medical device challenges to achieve common objectives and outcomes
  • Challenges are ill-defined or there is no consensus on the definition of the challenges
  • Challenges and outcomes are complex
  • Partners are interrelated
  • Incremental or unilateral efforts to address the challenge have been ineffective
  • Partners seek to optimize efforts, including preventing duplication of efforts
  • Better outcomes could be achieved with integrating different perspectives, experiences, resources, and expertise

Currently participates as a member of the five collaborative communities controlled by external stakeholders

  • Standardizing Laboratory Practices in Pharmacogenomics Initiative (STRIPE) 
  • International Liquid Biopsy Standardization Alliance (ILSA) 
  • Xavier Artificial Intelligence (AI) World Consortium


Efforts to Promote Patient Safety

Institute for Healthcare Improvement (IHI) and the Agency for Healthcare Research and Quality issued “Safer Together: A National Action Plan to Advance Patient Safety,” developed by the National Steering Committee (NSC) for Patient Safety. FDA actively involved with NSC.

4 approaches creating a culture of total systems safety

  • Culture, Leadership, and Governance: Commitments to safety as a core value
  • Patient and Family Engagement: Ensure meaningful partnership
  • Workforce Safety: Eliminate harm to both patients and the workforce
  • Learning System: Networked and continuous learning


Use of Drug Master Files to Further Support Cannabis Research  

Potential benefits of using Drug Master Files (DMFs) research on drugs containing cannabis and cannabis-derived compounds

  • Used to provide confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing
  • Allow 3rd parties to reference material (e.g., CMC) without disclosing DMF contents to those parties
  • Permits review of DMF information by FDA to support applications submitted by one or more applicants
  • DMF holder must provide a Letter of Authorization (LOA) and can have private agreements about information sharing, but FDA will not reveal any DMF contents to the applicant.


Image credits: FDA

COVID-19: Fraudulent products, Reference panel comparative data for assays, First Point-of-Care (POC) antibody test, Senate testimony, Infusion pump umbrella EUA revoked

Video: Beware of Fraudulent Coronavirus Tests, Vaccines and Treatments

Video explains:

  • There are currently no FDA-approved drugs or vaccines to treat or prevent COVID-19
  • Products that fraudulently claim to cure, treat, diagnose, or prevent COVID-19 haven’t been evaluated by the FDA for safety and effectiveness
  • They might be dangerous to you and your family
  • Fraudulent products can be reported to the FDA



SARS-CoV-2 Reference Panel Comparative Data

From February through the middle of May, the FDA issued a total of 59 EUAs for IVDs for the qualitative detection of nucleic acid from SARS-CoV-2

  • Reference Panel established to more precisely compare the performance of assays
  • Composed of standardized material, suitable for the determination and direct comparison of analytical sensitivity and cross-reactivity of nucleic acid-based SARS-CoV-2 assays


First Point-of-Care (POC) Antibody Test for COVID-19: Assure COVID-19 IgG/IgM Rapid Test Device

EUA USE: For POC use using fingerstick blood samples

ADDRESSING UNMET NEED: Fingerstick blood samples can now be tested in POC settings like doctor’s offices, hospitals, urgent care centers and emergency rooms rather than having to be sent to a central lab for testing


  • Lateral flow assay and is authorized for use with venous whole blood, serum, plasma and fingerstick whole blood
  • The test is authorized for the qualitative detection and differentiation of antibodies against SARS-CoV-2 indicating recent or prior SARS-CoV-2 (COVID-19) infection
  • This EUA authorizes the test for direct use with fingerstick blood samples in patient care settings, like doctors’ offices, hospitals, urgent care centers, and emergency rooms, rather than the samples being sent to a central laboratory for testing
  • Serology test results should not be interpreted to mean that a patient is immune to the virus or as an indication to stop taking steps to protect themselves and others against the spread of COVID-19


Testimony: Senate Committee on Health, Education, Labor and Pensions

Hearing entitled, “COVID-19: An Update on the Federal Response.” FDA Commissioner testimony described Agency’s efforts to protect the American public, help ensure the safety, efficacy, and quality of FDA-regulated medical products, and provide industries with tools and flexibility to do the same

  • Diagnostic testing
  • Vaccine development
  • Therapeutic development
  • Medical product supply (drugs & biological products, medical devices,
  • Inspections
  • Food supply
  • Fraudulent products


Umbrella Emergency Use Authorization of Infusion Pumps  Infusion Pump Accessories Revoked

FDA issued an umbrella EUA for infusion pumps and infusion pump accessories in May

  • For use by healthcare providers to treat COVID-19 conditions caused
  • For controlled infusion of medications, total parenteral nutrition (TPN), and/or other fluids
  • Included infusion pumps with remote monitoring or remote manual control features or administration sets and other accessories
  • However, no device has been added to the list of authorized devices

Current circumstances support revocation of the umbrella EUA

  • Individual EUAs will allow for tailored indications and scopes of authorization

EUA was revoked 

Image credit: FDA

COVID-19 News: Scientific, regulatory oversight of vaccine, Guidance on vaccine development, Guidance on manufacturing, Food-Cosmetics information center, Multilingual resources

FDA’s Scientific and Regulatory Oversight of Vaccines is Vital to Public Health

Committed to making decisions guided by science and data regarding the authorization or approval of COVID-19 vaccines. Guidance on Development and Licensure of Vaccines to Prevent COVID-19 (see below), additional guidance on EUA

Importance of diversity in clinical trial participants. FDA strongly encourages enrollment of all people – including racial and ethnic minorities, older adults, pregnant women and women of childbearing age and, as appropriate, children

FDA’s career scientists and physicians facilitating development and evaluation of safe and effective vaccines. Expertise in clinical trial design and analysis, adequacy of manufacturing and facilities for producing high-quality vaccines, and post-marketing safety surveillance

Importance of being as transparent as possible.  Public meeting of Vaccines and Related Biological Products Advisory Committee on October 22


GUIDANCE: Development and Licensure of Vaccines to Prevent COVID-19

Overview of key considerations to satisfy regulatory requirements per IND regulations and licensing regulations for chemistry, manufacturing, and controls (CMC), nonclinical and clinical data through development and licensure, and for post-licensure safety evaluation

CMC : General Considerations, Manufacture, Facilities, Inspections

Nonclinical data: Toxicity Studies, Immune Response characterization, Potential for Vaccine-associated Enhanced Respiratory Disease

Clinical trials: Populations, Design, Efficacy Considerations, Statistical Considerations, Safety Considerations

Either laboratory-confirmed COVID-19 or laboratory-confirmed SARS-CoV-2 infection is an acceptable primary endpoint

Primary efficacy endpoint point estimate for a placebo-controlled efficacy trial should be at least 50%

Post-licensure safety evaluation: Pharmacovigilance, Reqd post-marketing safety studies

Diagnostic and serological assays

Additional considerations: Vaccine effectiveness, EUA


GUIDANCE: Resuming Normal Drug and Biologics Manufacturing Operations During the COVID-19 Public Health Emergency

Guidance for manufacturers as they transition from operations impacted by the public health emergency to normal manufacturing operations. Recommendations include:

  • Addressing deviations from established cGMP activities
  • Risk Management and other important elements of a plan to resume normal drug manufacturing
  • Prioritizing activities to resume normal drug manufacturing


Food and Cosmetics Information Center (FCIC) Answers Your Questions

FCIC provides information and answers questions related to nutrition, safety, labeling of food, dietary supplements and cosmetics. Pandemic related, Complaints, Safety and Labeling, Expert advice


Multilingual COVID-19 Resources

CDC COVID-19 Communication Toolkit: For Migrants, Refugees, and Other Limited-English-Proficient Populations in various languages

Image credit: FDA

Other News and Views: Detection of nitrosamine contaminants, Trial stimulation before spinal cord stimulator implantation, Tanning beds and booths, Right to Try act, Naloxone prescribing

Rigorous Detection of Nitrosamine Contaminants in Metformin Products: Balancing Product Safety and Product Accessibility

Since 2018, multiple drug products, including angiotensin receptor blockers (ARBs), histamine blocker ranitidine (commonly known as Zantac), have been recalled due to the presence of nitrosamines at unacceptable amounts

  • CDER scientists have developed and publicly shared gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-MS (LC-MS) technologies
  • For detecting and quantifying up to eight different nitrosamines  at levels below acceptable U.S. intake limit for the nitrosaminat low levels


Conduct a Trial Stimulation Period Before Implanting a Spinal Cord Stimulator (SCS) 

Implanted SCS are an aid to cope with unmanageable, chronic chronic pain

  • However, FDA continues to receive reports of associated serious side effects

Health care providers should conduct a trial stimulation period with patients to confirm satisfactory pain relief before implanting a spinal cord stimulator (SCS)

  • Implant only in patients who have passed stimulation trial performed for 3-7 days showing 50% percent reduction in pain symptoms.
  • Discuss the benefits and risks of the different types of implants and other treatment options with patients
  • Several other recommendations


Tanning Beds and Booths

Tanning beds and booths are sunlamp products used for indoor UV skin tanning

  • Risk of fire due to improper maintenance, dirty air filters blocking air flow, incompatible parts, failure to perform servicing and maintenance
  • Owners and operators should perform maintenance recommended by product manufacturers to reduce risk of smoke and fire
  • FDA monitoring adverse event reports and will keep public informed


New Rule on Reporting Requirements for Right to Try Act

Right to Try Act provides pathway for patients with life-threatening diseases who have tried all approved treatment options and who are unable to participate in a clinical trial, to access certain unapproved treatments

  • Sponsor or manufacturer of drug/biologic is responsible for determining whether to make their product available to patients who qualify
  • New statutory requirement for sponsors and manufacturers to provide an annual summary to the FDA


Labeling Changes Regarding Naloxone

Naloxone can be administered by individuals with or without medical training to help reduce opioid overdose deaths

  • Required labeling changes recommend health care professionals prescribe naloxone when they prescribe medicines to treat OUD
  • Also, they consider prescribing naloxone to patients being prescribed opioid pain medicines who are at increased risk of opioid overdose


Image credit: FDA

Market Authorization, Warning: MONJUVI for B-cell lymphoma, TECARTUS for mantle cell lymphoma, EPIDIOLEX for tuberous sclerosis complex, VILTEPSO for duchenne muscular dystrophy, EVRYSDI for spinal muscular atrophy, WARNING for hangover remedies

MONJUVI® (tafasitamab-cxix) for injection

Morphosys Inc

INDICATION: in combination with lenalidomide, is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT).

MECHANISM OF ACTION: Tafasitamab-cxix is an Fc-modified monoclonal antibody that binds to CD19 antigen expressed on the surface of pre-B and mature B lymphocytes and on several B-cell malignancies, including DLBCL, mediates B-cell lysis through apoptosis and immune effector


  • Open label, multicenter single-arm trial, n=81 patients with a diagnosis of DLBCL
  • Endpoint: Overall response rate (ORR), defined as complete and partial responders and response duration
  • Best ORR : 55% (95% CI: 43%, 67%), complete responses in 37%, partial responses in 18%, median response duration was 21.7 months (range: 0, 24)

SAFETY: The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite.


  • Accelerated approval based on ORR, one month ahead of the FDA goal date.
  • Continued approval contingent upon verification and description of clinical benefit in a confirmatory trial(s)
  • Review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment
  • Priority review, fast track, breakthrough, and orphan product designation


TECARTUS™(brexucabtagene autoleucel) suspension for
intravenous infusion

Kite Pharma

INDICATION: CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL)

MECHANISM OF ACTION: Binds to CD19-expressing cancer cells, activate downstream signaling cascades that lead to T cell activation, proliferation, acquisition of effector functions , and
secretion of inflammatory cytokines and chemokines and to killing of CD19-expressing cells


  • Open-label, multicenter, single-arm trial, n=74 patients with relapsed or refractory MCL with prior therapy
  • Primary efficacy outcome measure: Objective response rate (ORR) based on a minimum duration of follow-up for response of six months
  • ORR was 87% (95% CI: 75, 94), with a complete remission (CR) rate of 62% (95% CI: 48, 74)
  • Of all 74 leukapheresed patients, ORR was 80% (95% CI: 69, 88) with a CR rate of 55% (95% CI: 43, 67)


  • Boxed Warning : Cytokine release syndrome and neurologic toxicities with a with a Risk Evaluation and Mitigation Strategy 
  • Most common Grade 3 or higher reactions: Anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection – pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia


  • Accelerated approval based on ORR and durability of response; continued approval contingent upon verification and description of clinical benefit in confirmatory trial
  • Orphan drug designation, breakthrough therapy designation, and priority review


Epidiolex (cannabidiol) [CBD] oral solution 

Greenwich Biosciences Inc.

INDICATION: Treatment of seizures associated with tuberous sclerosis complex (TSC) in patients one year of age and older

ADDRESSING UNMET NEED: Only FDA-approved drug that contains a purified drug substance derived from cannabis. It is also the second FDA approval of a drug for the treatment of seizures associated with TSC

  • TSC is a rare genetic disease causing non-cancerous (benign) tumors to grow in the brain and other parts of the body like the eyes, heart, kidneys, lungs, and skin
  • Affects about 1 in 6,000 people

MECHANISM OF ACTION: CBD is a chemical component of the Cannabis sativa plant. However, CBD does not cause intoxication or euphoria (the “high”) that comes from tetrahydrocannabinol (THC). Precise mechanism of anticonvulsant effect is unknown


  • Randomized, double-blind, placebo-controlled trial, n=224
  • Primary endpoint: Change from baseline in seizure frequency
  • Significantly greater reduction in the frequency of seizures with Epidiolex
  • Effect seen within eight weeks; consistent throughout the 16-week treatment period
  • Dispensed with patient Medication Guide with drug’s uses and risks
  • Most serious risks: Increase in suicidal thoughts and behavior, or thoughts of self-harm
  • Most common side effects: diarrhea, elevated liver enzymes, decreased appetite, sleepiness, fever, and vomiting
  • Additional side effects: liver injury, decreased weight, anemia, and increased creatinine


  • FDA supporting rigorous scientific research on the potential medical uses of cannabis-derived products and working with product developers who are interested in bringing patients safe and effective, high quality products
  • Previously approved for treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS)
  • Not a controlled substance 


VILTEPSO (viltolarsen) injection

NS Pharma

INDICATION: Treatment of Duchenne Muscular Dystrophy (DMD) in patients who
have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping

ADDRESSING UNMET NEED: DMD is a rare genetic disorder characterized by progressive muscle deterioration and weakness caused by mutations in the DMD gene that results in an absence of dystrophin. First symptoms are usually seen between three and five years of age and worsen over time. Occurs in approximately one out of every 3,600 male infants worldwide; in rare cases, it can affect females.

MECHANISM OF ACTION: Binds to exon 53 of dystrophin pre-mRNA resulting in exclusion of this exon during mRNA processing. Exon 53 skipping allows production of an internally truncated dystrophin protein in patients with genetic mutations that are amenable to exon 53 skipping


  • 2 clinical studies, n=32 patients with genetically confirmed DMD
  • Dystrophin levels increased, on average, from 0.6% of normal at baseline to 5.9% of normal at week 25
  • Increase in dystrophin production is reasonably likely to predict clinical benefit
  • Most common side effects: Upper respiratory tract infection, injection site reaction, cough and fever; kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides- function should be monitored


  • Accelerated approval; based on an increase in dystrophin production in skeletal muscle -continued approval contingent upon verification and description of clinical benefit


EVRYSDI™ (risdiplam) for oral solution


INDICATION: Treatment of Spinal Muscular Atrophy (SMA) in patients 2 months
of age and older

ADDRESSING UNMET NEED: SMA is a rare and often fatal genetic disease affecting muscle strength and movement; second drug and the first oral drug approved to treat disease

MECHANISM OF ACTION: Increases exon 7 inclusion in survival of motor neuron 2 (SMN2) messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein in the brain


  • Open-label, infantile-onset SMA study, n= 21 patients, average age 6.7 mo., 12 mo. treatment
  • Efficacy endpoint: Ability to sit without support for at least 5 sec and survival without permanent ventilation vs. natural progression of the disease
  • Meaningful improvement with 41% patients able to sit independently, 81% of patients were alive without permanent ventilation
  • Second randomized, placebo-controlled study, n=180 patients with later-onset SMA, age 2-25 yrs
  • Efficacy endpoint: Change from baseline in MFM32 (a test of motor function) total score at 1 yr; 1.36 increase in score with EVRYSDI vs. 0.19 decrease on placebo
  • Most common side effects: Fever, diarrhea, rash, ulcers of the mouth area, joint pain (arthralgia) and urinary tract infections
  • Additional side effects for the infantile-onset population: Upper respiratory tract infection, pneumonia, constipation and vomiting


  • Fast track designation, priority review, orphan drug designation,  Rare Pediatric Disease Priority Review Voucher


Hangover Remedies

Warning letters to seven companies whose products claim to cure, treat, mitigate, or prevent hangovers

  • Alcohol intoxication, a poisoning, causes dose-related dysfunction and damage, ranging from mild impairments to death
  • Products from these companies, labeled as dietary supplements, are unapproved new drugs and have not been evaluated by the FDA to be safe and effective for their intended use

Warning letters were sent to the following companies:


Image credits: FDA, Morphosys, Kite, Greenwich, NS Pharma, Genentech

COVID-19 News: BinaxNOW Ag Card + NAVICA app, Advisory Committee to discuss vaccine development, Convalescent plasma, Pooled sample testing and screening, Hand sanitizer warning

BinaxNOW COVID-19 Ag Card & NAVICA App

Abbott Diagnostics

INDICATION: Antigen test where results can be read directly from the testing card to manage risk by quickly identifying infectious people so they don’t spread the disease to others.  Authorized for use in patients suspected of COVID-19 by their healthcare provider within seven days of symptom onset. NAVICA™ app will allow people who test negative to display a temporary digital health pass that is renewed each time a person is tested through their healthcare provider together with the date of the test result

ADDRESSING UNMET NEED: First Diagnostic Test Where Results Can Be Read Directly From Testing Card

  • Highly portable (about the size of a credit card) and provides results in 15 minutes
  • Simple design is fast and efficient for healthcare providers and patients and does not need the use of an analyzer


  • Antigen test using lateral flow technology
  • A healthcare provider swabs the patient’s nose and twirls that sample on a test card with a testing reagent added
  • After waiting 15 minutes, the healthcare provider reads the results directly from the testing card. One line indicates a negative result; two lines indicate a positive result
  • Due to the potential for decreased sensitivity compared to molecular assays, negative results from an antigen test may need to be confirmed with a molecular test prior to making treatment decisions

REGULATORY PATHWAY: Emergency Use Authorization

  • Clinical study with several leading U.S. research universities demonstrated sensitivity of 97.1% (positive percent agreement) and specificity of 98.5% (negative percent agreement) in patients suspected of COVID-19 within the first seven days of symptom onset

 Abbott will sell this test for $5.


Advisory Committee Meeting to Discuss COVID-19 Vaccines

Public meeting of the Vaccines and Related Biological Products Advisory Committee will be held on Oct. 22, 2020

  • To discuss the general matter of the development, authorization, and/or licensure of vaccines indicated to prevent COVID-19
  • Assure that the process and review for vaccine development will be open and transparent
  • Committee made up of outside scientific and public health experts from around the country
  • Public discussion of clinical development of COVID-19 vaccines and data to support safety and effectiveness


VEKLURY (remdesevir)


INDICATION:  Treatment of all hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19, irrespective of their severity of disease.  Specifically, Veklury is only authorized for hospitalized adult and pediatric patients for whom use of an intravenous (IV) agent is clinically appropriate.

MECHANISM OF ACTION: Remdesivir is a nucleoside ribonucleic acid (RNA) polymerase inhibitor


  • One randomized, double-blind, placebo-controlled, n=1,062 hospitalized subjects with mild, moderate and severe COVID-19 who received Veklury (n=541) or placebo (n=521), median time to recovery from COVID-19 was 10 days for the Veklury group compared to 15 days for the placebo group. In hospitalized patients with mild to moderate disease, the results for time to recovery as well as the odds of improvement at Day 15 numerically favored the Veklury group and were consistent with the overall study results.
  • A separate randomized, open-label multi-center trial,  hospitalized adult subjects with moderate COVID-19 treatment with Veklury for five days (n=191) and treatment with Veklury for 10 days (n=193) with standard of care (n=200). Odds of subject’s COVID-19 symptoms improving were statistically significantly higher in the five-day Veklury group at Day 11 when compared to those receiving only standard of care. The odds of improvement with the 10-day treatment group when compared to those receiving only standard of care were numerically favorable, but not statistically significantly different
  • Possible side effects include: increased levels of liver enzymes, which may be a sign of inflammation or damage to cells in the liver; and infusion-related reactions, which may include low blood pressure, nausea, vomiting, sweating, and shivering.



Convalescent Plasma

Convalescent plasma from individuals who have recovered from COVID-19 has not been approved for use by FDA, so it is regulated as an investigational product


Pooled Sample Testing and Screening Testing

FDA encouraging the development of tests for screening asymptomatic individuals and for testing pooled samples

  • Involves mixing several samples together in a “batch” or pooled sample, then testing the pooled sample with a diagnostic test
  • Increases the number of individuals that can be tested using same amount of resources
  • However, because samples are diluted, which could result in less viral genetic material available to detect, there is a greater likelihood of false negative results
  • Works well when there is a low prevalence of cases, meaning more negative results are expected than positive results
  • Several resources being provided


Warning: Hand Sanitizer Packaged in Food and Drink Containers

FDA warning consumers about alcohol-based hand sanitizers that are being packaged in containers that may appear as food or drinks

  • Being packaged in beer cans, children’s food pouches, water bottles, juice bottles and vodka bottles
  • Containing food flavors, such as chocolate or raspberry
  • May put consumers at risk of serious injury or death if ingested


Image credit: Abbott, Gilead, FDA

COVID News: SalivaDirect, Device shortage list, Your digital health, Hand sanitizer warning, Steps to stop spread, Convalescent plasma toolkit


Yale School of Public Health

INTENDED USE & DESCRIPTION: For rapid detection of SARS-CoV-2 using saliva instead of respiratory swabs, which enables non-invasive frequent sampling and reduces the need for trained healthcare professionals during collection.


  • With different combinations of commonly used reagents and instruments, meaning the test could be used broadly in most high-complexity labs
  • Yale intends to provide the SalivaDirect protocol to interested laboratories as an “open source” protocol
  • Because this test does not rely on any proprietary equipment from Yale and can use a variety of commercially available testing components, it can be assembled and used in high-complexity labs throughout the country, provided they comply with the conditions of authorization in the EUA

REGULATORY PATHWAY: Emergency Use Authorization (EUA)

  • Fifth test that uses saliva as a sample for testing


Device Shortage List

FDA monitoring healthcare landscape and supply chain for resulting shortages, or meaningful disruptions to U.S. supply, of certain medical devices

  • Manufacturers of certain devices notify FDA of permanent discontinuance in manufacture of the device
  • Interruption in the manufacture of device that is likely to lead to meaningful disruption in supply during declared public health emergency
  •  Categories of devices in the device shortage list are (1) Personal Protective Equipment (2) Testing Supplies and Equipment (3) Ventilation-Related Products

Device shortage and discontinuance list

FDA Insights: Your Digital Health

Discission on telemedicine, digital health tools, and FDA’s new Digital Health Center of Excellence

Listen , Digital Health page

Hand Sanitizers Consumers Should Not Use

Hand sanitizer products labeled to contain ethanol or isopropyl alcohol but have tested positive for 1-propanol and methanol contamination

  • Young children, adolescents and adults who drink these products as an alcohol (ethanol) substitute are at risk
  • Can cause central nervous system (CNS) depression, which can result in death
  • Exposure can include confusion, decreased consciousness, and slowed pulse and breathing
  • Skin or eye exposure can result in irritation, and rare cases of allergic skin reactions have been reported.


Help Stop the Spread of Coronavirus and Protect Your Family

Remain vigilant and take simple steps

  • Wash Your Hands
  • Wear a Mask and Avoid Crowds 
  • Save Personal Protective Equipment for Those on the Front Lines
  • Follow Food Safety Guidelines
  • Donate Blood 
  • If You Have Fully Recovered From COVID-19, Donate Plasma
  • Report Fraudulent Coronavirus Tests, Vaccines, and Treatments


The Fight Is In Us: Convalescent Plasma Fact Sheets and Toolkit

FDA working together with health care organizations and other partners to slow spread and meeting the challenge of COVID-19

Image credits: Yale, FDA

FDA COVID News: Operation Quack Hack for fraud prevention, Test for IgG antibodies from previous infection, Test for screening prople without known infection, Advanced manufacturing for preparedness, Plasma donation, COVID and Cancer website

FDA Protects Patients and Consumers from Fraud During COVID-19

Operation Quack Hack leverages agency expertise and advanced analytics to protect consumers from fraudulent medical products during the COVID-19 pandemic

  • As of June 2020, team has identified more than 700 fraudulent and unproven medical products 
  • Has reviewed thousands of websites, social media posts, and online marketplace listings
  • > 90 warning letters to sellers, more than 150 reports sent to online marketplaces, and more than 250 abuse complaints sent to domain registrars to date.


First Tests to Estimate Patient’s IgG Antibodies from Past SARS-CoV-2 Infection

ADVIA Centaur COV2G and Atellica IM COV2G, Siemens

COVID-19 serology tests to estimate quantity of antibodies present in the individual’s blood

  • Useful tool to evaluate antibodies to a previous COVID-19 infection
  • Still many unknowns about what the presence of SARS-CoV-2 antibodies and potential immunity
  • Patients cautioned against using the results as an indication to stop taking steps to protect themselves and others
  • Instructions for Use

Advanced Manufacturing to Support Public Health Preparedness

Many medical products are still being manufactured using outdated technologies

  • Can increase the risk of shortages, limit flexibility during an emergency, and contribute to high cost
  • Encouraging “advanced manufacturing,” which refers to new and emerging approaches for production of medical technologies
  • Examples include process intensification methods, such as continuous manufacturing, 3D printing can help produce patient-specific medical devices, digital and smart design and manufacturing processes to increase efficiency and reduce uncertainty
  • READ

First Diagnostic Test for Screening of People Without Known or Suspected COVID-19 Infection

LabCorp COVID-19 RT-PCR Test EUA

For testing people who do not have COVID-19 symptoms or who have no reason to suspect COVID-19 infection, and to allow pooled sample testing 

  • Step toward the type of broad screening that may help enable the reopening of schools and workplaces
  • Also test pooled samples containing up to five individual swab specimens collected under observation
  • Help receiving results sooner, while also conserving vital testing supplies
  • Prescription-only and is authorized for human specimen collection either at home or by a health care provider
  • Only health care provider-collected samples may be pooled at this time
  • Test is as accurate in the broader asymptomatic population as it is among people suspected to have COVID-19
  • EUA Summary

If you have recovered from COVID-19, confirmed by a positive test, you’re in a special position to help us fight the virus. Donate plasma now

New Website on Cancer and COVID-19

FDA Oncology Center of Excellence recognizes cancer patients constitute a vulnerable population at risk ; current priorities

  • Expedite oncology product development
  • Recognize that modifications may be required in clinical trials
  • Innovating collection and analysis of real-world evidence on patient outcomes
  •  Process Expanded Access requests for investigational products
  • Anticipate and prevent drug shortages
  • Inform the cancer community

Cancer and COVID-19

Image credits: FDA, Labcorp, Siemens

COVID-19 updates: Test for pooled samples, CTAP, Domestic inspections, FDA Insights podcasts, Laboratory and Manufacturer resources


Quest SARS-CoV-2 rRT-PCR test for pooled samples

Quest Diagnostics

Emergency Use Authorization for first diagnostic test use with pooled samples containing up to four individual swab specimens

  • Sample pooling allows for more people to be tested quickly using fewer testing resources
  • Samples collected from four individuals tested in pool or “batch” using one test, rather 4 tests
  • If pool is positive, each of the samples in that pool are tested again individually
  • Fewer tests are run overall, meaning fewer testing supplies and quicker test particulalry in areas with low prevalence, meaning most results are expected to be negative.

Package insert

Coronavirus Treatment Acceleration Program

The Coronavirus Treatment Acceleration Program (CTAP) to enable FDA to leverage cross-agency scientific resources and expertise to bear on COVID-19 drugs and biologics development and review


Resumption of domestic inspections with new risk assessment system

COVID-19 Advisory Rating system (COVID-19 Advisory Level) to assist in determining when and where it is safest to conduct prioritized domestic inspections

  • Uses real-time data to qualitatively assess the number of COVID-19 cases in a local area based on state and national data
  • Phase of the State, statistics measured at the county level to gauge the current trend and intensity of infection
  •  Goal of restarting on-site inspections during the week of July 20


FDA Insights podcasts

Insight into issues facing the agency – including the COVID-19 pandemic and other emerging topics.


COVID-19 Resources for Laboratories and Manufacturers

Emergency Use Authorizations for Medical Devices

EUA Authorized Serology Test Performance

Independent Evaluations of COVID-19 Serological Tests

Testing Supply Substitution Strategies: Download the slide show file (PPT – 1.5MB) and click Slide Show > From Beginning.

Reporting fraudulent products

Image credit: FDA

Marketing Authorizations: EndeavorRX digital therapy for ADHD, FINTEPLA for Dravet Syndrome, GALLANT defibrillator systems

EndeavorRx digital therapy

Akili Interactive

INDICATION FOR USE: Digital therapeutic indicated to improve attention function as measured by computerbased testing in children ages 8-12 years old with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue. Patients who engage with EndeavorRx demonstrate improvements in a digitally assessed measure Tests of Variables of Attention (TOVA) of sustained and selective attention and may not display benefits in typical behavioral symptoms, such as hyperactivity. EndeavorRx should be considered for use as part of a therapeutic program that may include: clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder.

DEVICE TYPE: Digital therapy device for Attention Deficit Hyperactivity Disorder. Software intended to provide therapy for ADHD or any of its individual symptoms as an adjunct to clinician supervised treatment.

ADDRESSING UNMET NEED: First digital therapeutic intended to improve symptoms associated with ADHD. First game-based therapeutic granted marketing authorization by the FDA for any type of condition. 


  • Multiple studies in >600 children
  • Evaluated demonstrated improvements in attention function, as measured by TOVA, academic performance measures, and other assessment tools
  • No serious adverse events reported
  • Most common adverse events: Frustration, headache, dizziness, emotional reaction, and aggression

REGULATORY PATHWAY: De Novo classification

Reclassification order

FINTEPLA (fenfluramine) oral solution

Zogenix Inc

INDICATION: Treatment of seizures associated with Dravet syndrome in patients 2 years of age and older

MECHANISM OF ACTION: Exact mechanism for treatment of seizures unknown;
fenfluramine and metabolite, norfenfluramine, increase extracellular levels of serotonin and exhibit agonist activity at serotonin 5HT-2 receptors

ADDRESSING UNMET NEED: New therapy for Dravet syndrome- a life-threatening, rare and chronic form of epilepsy that is characterized by severe and unrelenting seizures despite medical treatment


  • Two clinical studies, n=202 subjects 2-18 years old; Fintepla vs placebo
  • Primary endpoint: Change from baseline in the frequency of convulsive seizures
  • Significantly greater reductions in convulsive seizures frequency with Fintepla within 3-4 weeks, remained consistent over the 14- to 15-week treatment periods
  • Boxed warning: Valvular heart disease (VHD) and pulmonary arterial hypertension (PAH)
  • Most common adverse reactions: Decreased appetite; drowsiness, sedation and lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue or lack of energy; ataxia, balance disorder, gait disturbance, blood pressure; drooling, salivary hypersecretion, pyrexia; upper respiratory tract infection; vomiting; decreased weight; risk of falls; and status epilepticus.


  • Priority Review, Orphan Drug Designation
  • Schedule IV controlled substance
    • Restricted drug distribution program, REMS)
    • Special certification to dispense, cardiac monitoring with echocardiograms


GALLANT implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D) devices 


INDICATION FOR USE: For automated treatment of life-threatening ventricular arrhythmias; also indicated to treat symptoms in patients who have congestive heart failure with ventricular dyssynchrony. In addition, dual chamber ICD and CRT-D devices with the AT/AF detection algorithm are indicated in patients with atrial tachyarrhythmias or those patients who are at significant risk of developing atrial tachyarrhythmias.
MR Conditional ICDs and CRT-Ds are conditionally safe for use in the MRI environment when used in a complete MR Conditional system and according to instructions in the MRI-Ready Systems manual. Scanning under different conditions may result in severe patient injury, death or device malfunction.
The myMerlinPulse™ mobile application is indicated for use by patients with supported Abbott Medical implanted heart devices.


  • Implantable Cardioverter Defibrillator (ICD) and Cardiac Resynchronization Therapy Defibrillator (CRT-D) device intended to provide ventricular antitachycardia pacing and ventricular cardioversion/defibrillation; also intended to resynchronize right and left ventricles
  • Pairs with Abbott’s secure myMerlinPulse™, an iOS- and Android™- compatible mobile smartphone app that helps streamline communication between doctors and their patients
  • App provides people with access to data, device performance, and transmission history, which helps them take an active role in their healthcare
  • Through the app, physicians can continuously monitor their patients remotely allowing for identification of asymptomatic episodes as well as patient-triggered transmissions, which can lead to earlier intervention and reduce clinical burden


  • 6.1 million people in US with cardiac arrhythmias, or abnormal heart rhythms
  • ICDs are used to help reduce the risks of life-threatening arrhythmias.
  • CRT-Ds can be used to restore the heart’s natural pattern of beating for patients with heart failure or in situations when the heart’s chambers beat out of sync


Safety Information

Image credits: Akili, Zogenix, Abbott

COVID News: Hydroxychloroquine sulfate/ chloroquine phosphate revocation, Vaccine development guidance, Partnering with EU, Warning against methanol containing hand sanitizers

Revocation of EUA for hydroxychloroquine sulfate (HCQ) and chloroquine phosphate (CQ) to treat COVID-19

FDA believe’s the suggested dosing regimens for CQ and HCQ unlikely to produce an antiviral effect

  • Earlier observations of decreased viral shedding with HCQ or CQ treatment have not been consistently replicated
  • Recent data from a randomized controlled trial showed no difference between HCQ vs. standard of care slone
  • Current U.S. treatment guidelines do not recommend the use of CQ or HCQ outside of a clinical trial; NIH guidelines now recommend against such use outside of clinical trial
  • Recent data from a large randomized controlled trial with HCQ showed no evidence of benefit for mortality or hospital length of stay or need for mechanical ventilation
  • Additionally, the serious cardiac adverse events and other serious side effects cause the risks to outweigh benefits

Frequently Asked Questions on the Revocation of the Emergency Use Authorization for Hydroxychloroquine Sulfate and Chloroquine Phosphate (PDF, 125 KB)


Development and Licensure of COVID-19 vaccine

Recommendations :

  • Using different technologies such as DNA, RNA, protein and viral vectored vaccines
  • Help expedite vaccine development without sacrificing our standards for quality, safety, and efficacy
  • Guidance provides overview of key considerations chemistry, manufacturing and control, nonclinical and clinical data
  • Studies to directly evaluate the ability of the vaccine to protect humans from SARS-CoV-2 infection and/or disease

Final Guidance

Partnering with the European Union and Global Regulators on COVID-19

FDA, European Commission (EC) and European Medicines Agency (EMA) have a multitude of critical scientific and regulatory collaborations for COVID-19 response  

  • 30 technical expert groups, or “clusters”
  • Exchanging information on interpretation of data supporting regulatory decisions
  • Virtual bilateral meetings to review high-priority areas
  • Engagement with global regulators, under the International Coalition of Medicines Regulatory Authorities (ICMRA) forum, which is comprised of 28 regulatory authorities from around the globe
  • International collaborations in medical device work
  • READ

Action to Warn, Protect Consumers from Dangerous Alcohol-Based Hand Sanitizers Containing Methanol

Hand sanitizer products containing methanol, or wood alcohol

  • Often used to create fuel and antifreeze
  • Can be toxic when absorbed through the skin as well as life-threatening when ingested
  • Reported recent adverse events from adults and children including blindness, hospitalizations and death


Webpage for a full list of FDA-tested and recalled hand sanitizers:

Image credit: FDA

COVID-19 update: FDA Commissioner reflections, Innovations to respond, Testing basics, Hospital beds- stretchers-mattresses, Educational resources, Updated scientific FAQs on testing

The COVID-19 Pandemic — Finding Solutions, Applying Lessons Learned

Reflections from 24th FDA Commissioner Dr. Stephen Hahn

  • Inability to control the events that affect our lives
  • History teaches us that crises often lead to accelerated change and innovations and new discoveries
  • FDA continuously innovating and accelerating measures-for food, drug, devices, diagnostics- to respond to pandemic
  • Learnings will influence FDA functioning post-pandemic


Innovation to Respond to COVID-19

Connect Manufacturers and Health Care Entities: Facilitating information-sharing regarding the use of 3D printing and other advanced manufacturing technologies in the context of personal protective equipment (PPE) and other medical device parts

 Collaborations to Promote Real-World Data Analysis : Harness diverse streams of data to understand and respond to COVID-19 with the potential to contribute to the scientific evaluation of potential diagnostics and interventions

Coronavirus Treatment Acceleration Program (CTAP) : Special emergency program to accelerate new treatments to patients as quickly as possible, while at the same time finding out safety and effectiveness.

Guidance Documents to Support Innovators and Researchers : To accelerate development of prevention and treatment options, increase efficiency of initiating new trials with recommendations for clinical trial designs

COVID-19 Testing Basics

FDA information on different categories of tests

  • Diagnostic Test: Can show if you have an active coronavirus infection and should take steps to quarantine or isolate yourself from others. Currently there are two types of diagnostic tests – molecular (RT-PCR) tests that detect the virus’s genetic material, and antigen tests that detect specific proteins on the surface of the virus.
  • Antibody test: Looks for antibodies that are made by the immune system in response to a threat, such as a specific virus. Antibodies can help fight infections. Antibodies can take several days or weeks to develop after you have an infection and may stay in your blood for several weeks after recovery. Because of this, antibody tests should not be used to diagnose an active coronavirus infection. At this time researchers do not know if the presence of antibodies means that you are immune to the coronavirus in the future.


COVID-19: Hospital Beds, Stretchers, and Mattresses

Information to manufacturers of hospital beds, stretchers, and mattresses to meet increased demand

  • How to know of potential shortage in advance or reporting shortages
  • How does FDA regulate hospital beds, stretchers, and mattresses and what are the guidances
  • What are applicable recognized consensus standards
  • Claims of antimicrobial or antiviral properties
  • Requirements regarding new and non-traditional supply chain partners


COVID-19 Educational Resources

FAQs on Testing for SARS-CoV-2

Image credit: FDA

COVID-19 update: Product terminology, First Standalone at-home sample collection kit , COVID MyStudies App, Guidance to streamline test development, Cancer doctor’s perspective: hydroxychloroquine and chloroquine, Updated EUAs

FDA Terminology of COVID-19 Potential Preventions and Treatments

  • FDA Approved: Independent scientific reviews to determine safety and effectiveness for its intended use and manufactured according to federal quality standards
  • Investigational Treatment:  Experimental- to study use in diease/condition, safety, dose, benefits and risks
  • Expanded Access: Potential pathway for patient with serious/immediately life threatening disease to gain access to investigational product outside of clinical trials
  • Emergency Use Authorization (EUA): Different than approval or clearance; product availability based on the best available evidence, without waiting for all the evidence. Effective until emergency declaration ends

First Standalone At-Home Sample Collection Kit 

Everlywell COVID-19 Test Home Collection Kit

INDICATION: For use by individuals to self-collect nasal swab specimens at home, when determined by a healthcare provider to be appropriate based on results of a COVID-19 questionnaire, and for use only with in vitro diagnostic (IVD) molecular tests for the detection of
SARS-CoV-2 RNA that are indicated for use with the Everlywell COVID-19 Home Collection Kit


  • Used by individuals at home screened via online questionnaire & reviewed by health care provider
  • Self-collect a nasal sample at home using Everlywell’s authorized kit (nasal swabs and tube filled with saline to transport the sample back to a specified lab)
  • Samples tested by specific CLIA-certified laboratories each with individual EUAs to test Everlywell at-home sample collection kit (Fulgent Therapeutics, Assurance Scientific Laboratories)
  • Results to patient through Everlywell’s independent physician network and online portal


  • Data from studies supported by The Bill and Melinda Gates Foundation and UnitedHealth Group to demonstrate stability of specimens during shipping
  • Study data freely available to support other EUA requests, alleviating burden of recreating the same study 


COVID MyStudies App

  • Free platform to remotely obtain informed consent from patients in COVID-19 trials
  • To assist with clinical trials when patients are in or unable to outpatient clinics
  • In Apple App and Google Play


Guidance on Steps to Streamline Development of Tests

  • Steps to further support development of COVID-19 tests for at-home self-collection
  • Voluntary  EUA Template for at-home sample collection kits
  • Template reflects FDA’s current thinking on data and information that developers should submit to facilitate EUA process
  • Includes recommendations for use by laboratories and commercial manufacturers
  • Applies to EUA as well as part of an Institutional Review Board (IRB)-approved study


Cancer Doctor’s Perspective: Hydroxychloroquine and Chloroquine

FDA plays pivotal role to provide new medical products to patients as soon as possible, while at the same time determining effectiveness and if benefits outweigh the risks

Drugs hydroxychloroquine and chloroquine have received particular attention

  • Both are FDA-approved to treat or prevent malaria, and hydroxychloroquine is also approved to treat autoimmune conditions such as chronic discoid lupus erythematosus, systemic lupus erythematosus in adults, and rheumatoid arthritis – have a well-established safety profile for these conditions
  • NOT approved to prevent or treat COVID-19 – subject of numerous clinical trials
  • FDA neither endorses individual prescribing decisions nor prohibits physicians from prescribing
  • It is important that patients and health care providers understand side effects including serious and potentially life-threatening heart rhythm problems as noted in a recent Drug Safety Communication
  • FDA issued EUA that allowed for treatment of certain hospitalized COVID-19 patients for whom a clinical trial is not available, or participation is not feasible
  • Will continue to look at the data to make future determinations on these products based on available evidence including ongoing clinical studies


Updated page on current and terminated Emergency Use Authorizations for COVID-19

Image credit: FDA

COVID-19 updates: Facilitating development and availability of medical products, New actions to accelerate development of novel treatment options, Surveillance inspections


Facilitating development and availability of medical devices

Working to facilitate development and availability of medical products for patients, physicians, healthcare systems as expeditiously and safely as possible

  • Emergency Use Authorizations (EUAs): Quickly allowing unapproved medical products to reach patients in need when there are no adequate, FDA-approved alternatives
  • Deal with supply issues
  • Updated website


Facilitating development and availability of drugs 

Coronavirus Treatment Acceleration Program (CTAP) to expedite the development of potential COVID-19 therapies

  • Several therapies currently being tested in clinical trials to evaluate whether
    they are safe and effective in combating COVID-19
  • National effort to facilitate the development of, and access to, investigational therapies derived from human blood
  • Make treatment options available to patients and providers who are not able to participate in clinical trials through expanded access under investigational drug (IND) applications


New Actions to Accelerate Development of Novel Prevention, Treatment Options for COVID-19

> 130 clinical trials of potential COVID-19 related treatments and additional development programs for other agents are in the planning stages

  •  FDA has started to receive data from clinical studies and expects to receive more
  • Agency intends to engage with pharmaceutical sponsors and other government partners for expedited patient access when favorable results

2 Guidances


Surveillance inspections during COVID-19

CDC collaboration to develop a process to return to on-site facility surveillance inspections in accordance with White House Guidelines for ‘Opening Up America Again’

  • First protect health and well-being of workforce and state contract inspectors as well as industry  health of workers
  • Communications with industry as well as domestic and foreign regulatory counterparts
  • Leadership team meet daily to discuss the urgent issues related to drugs/devices, medical and food product supply chains, leverage public health tools
  • Closely monitor global situation and remain in contact with domestic and foreign regulatory counterparts




COVID-19 Updates: First Antigen Test for rapid detection, First Diagnostic Test using at-home saliva collection, Documents for Reopening, Updated COVID-19 resources


Sofia 2 SARS Antigen FIA
First Antigen Test to Help in Rapid Detection of COVID-19 virus

Quidel Corporation

INDICATION: Qualitative detection of the nucleocapsid protein antigen from SARS-CoV-2 in nasopharyngeal (NP) and nasal (NS) swab specimens directly


  • New category of tests for use in ongoing pandemic
  • Quick detection of protein fragments found on or within the virus


  • Lateral flow immunofluorescent sandwich assay for the qualitative detection of nucleocapsid protein antigen from SARSCoV-2 in nasopharyngeal (NP) and nasal (NS) swab specimens
  • SARS-CoV-2 nucleocapsid protein antigen is generally detectable in respiratory specimens during the acute phase of infection
  • Positive results are indicative of presence of SARS-CoV-2 nucleocapsid protein antigen, but clinical correlation with patient history and other diagnostic information is necessary to determine infection status
  • Negative results should be treated as presumptive and confirmed with a molecular assay

REGULATORY PATHWAY: Emergency Use Authorization


First Diagnostic Test Using At-Home Collection of Saliva Specimens

TaqPath SARS-CoV-2 Assay

Rutgers Clinical Genomics Laboratory

Spectrum Solutions LLC SDNA-1000 Saliva Collection Device

INDICATION: Qualitative detection of nucleic acid from SARS-CoV-2 in oropharyngeal (throat) swab, nasopharyngeal swab, anterior nasal swab, mid-turbinate nasal swab, and bronchoalveolar lavage (BAL) fluid from individuals.  This test is for use with saliva specimens that are self-collected at home with the LLC SDNA -1000 collection device

ADDRESSING UNMET NEED: First diagnostic test where nasal specimens can be collected at home


  • Qualitative test for detection of nucleic acid from SARS-CoV-2
  • Self-collection saliva specimens at home or in a healthcare setting
  • SARS-CoV-2 nucleic acid generally detectable in respiratory specimens during the acute phase of infection
  • Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to
    determine patient infection status
  • Positive results do not rule out bacterial infection or coinfection with other viruses

REGULATORY PATHWAY: Emergency Use Authorization



Documents to support Reopening

FDA issued documents designed to assist retail food establishments in preparing to reopen

  • Help businesses that prepare food to serve or sell to the public directly, such as restaurants, bakeries, bars and carry-outs, protect employee and public health as they reopen for business

Food Safety Checklist


Updated COVID-19 Resources

FAQs on Testing for SARS-CoV-2

FDA COVID-19 Response: At-A-Glance Summary

Image credit: FDA

COVID-19 Updates: Remdesivir, Convalescent plasma, Tips & FAQs (EUAs, Alcohol-based hand sanitizer, Medical Countermeasures Initiative, Grocery shopping, Pet safety


REMDESIVIR injection


AUTHORIZED USE: Treatment of patients hospitalized with suspected or laboratory confirmed SARS-CoV-2 infection and severe disease.

Severe disease is defined as patients with an oxygen saturation (SpO2) ≤94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). Specifically, remdesivir is only authorized for hospitalized adult and pediatric patients for whom use of an intravenous agent is clinically appropriate.

MECHANISM OF ACTION: Nucleoside ribonucleic acid (RNA) polymerase inhibitor that inhibits viral RNA synthesis; activity in cell culture and animal models against SARS-CoV, MERS-CoV, and SARS-CoV-2


NIAID-sponsored randomized, double-blinded, placebo-controlled trial

  • Randomized, double-blind, placebo-control, remdesivir vs. placebo, n= 1063 hospitalized patients
  • Primary clinical endpoint: Time to recovery within 28 days after randomization
  • Preliminary analysis:  Median time to recovery was 11 days (remdesivir) vs. 15 days (placebo) p<0.001), Mortality was 8.0% (remdesivir) vs. 11.6% (placebo), p=0.05

Gilead-sponsored open-label trial

  • Randomized, open-label multi-center clinical trial, n~400 with severe COVID-19 with 5-day or 10-day treatment
  • Primary clinical endpoint: Clinical status assessed by 7-point ordinal scale at Day 14 after randomization
  • Preliminary Analysis: Similar improvement in clinical status in both groups


  • Hepatic adverse reactions: Transaminase elevations, ALT and AST, need for appropriate clinical and laboratory monitoring

REGULATORY PATHWAY: Emergency Use Authorization

  • SARS-CoV-2 can cause  serious or life-threatening disease or condition
  • Based on the totality of scientific evidence available to FDA, it is reasonable to believe that remdesivir may be effective in treating COVID-19
  • There is no adequate, approved, and available alternative to the emergency use of
    remdesivir for the treatment of COVID-19



Investigational COVID-19 convalescent plasma

Providing  recommendations to health care providers and investigators on the administration and study of investigational convalescent plasma

Donor eligibility

  • Evidence of COVID-19 documented by a laboratory test or positive serological test
  • Complete resolution of symptoms at least 14 days before donation
  • SARS-CoV-2 neutralizing antibody titers, if available

Patient eligibility

  • Laboratory confirmed COVID-19
  • Severe or immediately life-threatening COVID-19
  • Informed consent



COVID-19 Tips and FAQs

What is Emergency Use Authorization

Updated EUA Webpage

Availability of alcohol-based Hand sanitizer

Medical Countermeasures Initiative (MCMi)

12 tips for grocery shopping

Pet safety

Image credit: Gilead, FDA

COVID-19 Updates: At-a-glance resource, Caution on Hydroxychloroquine or Chloroquine use, Remote digital pathology devices


FDA COVID-19 RESPONSE: At-a-Glance Summary

Major focus areas

  • Testing, therapeutics, and devices such as ventilators and personal protective equipment
  • Vaccine development
  • Food supply
  • Action on fraudulent products


Cautions against use of hydroxychloroquine or chloroquine for COVID-19 due to risk of heart rhythm problems

  • Reports of serious and potentially life-threatening heart rhythm problems
  • May be mitigated when health care professionals closely screen and supervise COVID-19 patients in a hospital setting or a clinical trial


Remote Digital Pathology Devices During COVID-19 Emergency

Guidance to help expand the availability of digital pathology devices for remote reviewing and reporting of scanned digital images of pathology slides during this pandemic

  • Automated Digital Image Manual Interpretation Microscope
  •  Whole Slide Imaging System
  • Digital Pathology Image Viewing and Management Software
  • Digital Pathology Display

Expanded, off-label use for the duration of the COVID-19 public health emergency

  • Facilitate remote reviewing and reporting of pathology slides
  • Help facilitate continuity of patient care
  • Reduce healthcare personnel contact and risk of exposure


Image credit: FDA

COVID-19 Updates


ACTIV Public-private partnership to speed COVID-19 vaccine and treatment options

NIH announced ‘Accelerating COVID-19 Therapeutic Interventions and Vaccines’ (ACTIV) partnership with FDA and others to speed the development of COVID-19 vaccine and treatment options

  • Standardize and share preclinical evaluation methods in open forum allowing for comparison and validation
  • Prioritize and accelerate clinical evaluation of therapeutic candidates with near-term potential
  • Maximize clinical trial capacity and effectiveness
  • Advance vaccine development


Protecting Public Health from Fraudulent and Potentially Harmful Products

Temporary injunction against the Genesis II Church of Health and Healing (Genesis)

  • Unlawfully distributing MMS: When combined with included activator, has a chlorine dioxide content equivalent to industrial bleach
  • There is danger that defendants will continue violating the law without temporary restraining order; defied previous Warning letter

Warning letter to Nova Botanix LTD DBA CanaBD

  • Selling unapproved and misbranded cannabidiol (CBD) product deliberately misleading claims for prevention and treatment of COVID-19
  • Currently NO FDA-approved products to prevent or treat COVID-19

Expansion of COVID-19 Testing by Using Synthetic Swabs 

FDA, Gates Foundation, UnitedHealth Group, Quantigen, U.S. Cotton Collaborate to Address Testing Supply Needs

Synthetic swabs – with a design similar to Q-tips – could be used to test patients by collecting a sample from the front of the nose

U.S. Cotton

  • Developed polyester-based, synthetic Q-tip-type swab  for compatibility with COVID-19 testing
  • Plans to produce the new swabs in large quantities for increased diagnostic testing

UnitedHealth Group, Quantigen, Gates Foundation

  • Clinical investigation to support synthetic swab use
  • Testing to support swabbing at  front of nose used enabling more comfortable, self-collection by patients and limiting exposure of healthcare providers


Emergency Use Authorization (EUA): Seraph 100 Microbind Affinity Blood Filter device

INDICATION FOR USE: Extracorporeal blood purification (EBP) device) to treat patients 18 years of age or older with confirmed COVID-19 admitted to the ICU with confirmed or imminent respiratory failure to reduce pathogens and inflammatory mediators from the bloodstream

  • Designed to reduce bacteria, viruses, toxins, cytokines and other inflammatory mediators from whole blood
  • Form factor very similar to other blood filters, such as hemodialyzers or hemoperfusion filters – compatible with hemodialysis systems that use industry standard bloodline connectors for ease of operation, training, and utility


COVID-19 Diagnostics Update


Coronavirus pandemic and making a difference


Make a Difference During the Coronavirus Pandemic

FDA suggested ways for you and your family to make a difference

  • Protect Yourself and Others
  • Donate Blood
  • Donate Plasma if fully recovered from COVID-19
  • Report fraudulent Tests, Vaccines, and Treatments
  • Save Personal Protective Equipment for those on the front lines
  • Reduce Food panic-buying
  • Clean Hands often

More information 


Image credit: FDA

FDA COVID-19 actions


FDA COVID-19 updates

The Agency is playing an integral role in the coronavirus fight, using science and innovative approaches as well as joining in the healthcare frontlines

Here are some of the recent actions

Coronavirus Treatment Acceleration Program (CTAP)


Coronavirus Treatment Acceleration Program (CTAP)

 Special emergency program for possible therapies – to be updated real time


  • 10 therapeutic agents in active trials
  • Another 15 therapeutic agents in planning stages


  • Rapid responses to queries, ultra-rapid review of protocol, development plans
  • Review single patient expanded access requests within 3 hours



FDA COVID-19 Updates


Coronavirus Disease 2019 (COVID-19)

FDA is working with U.S. Government partners, including CDC, and international partners to address the coronavirus disease 2019 (COVID-19) outbreak

Read about

Or search


Includes links to CDC, OSHA and


Image credit: FDA

Fraudulent COVID-19 Products


Beware of Fraudulent Coronavirus Tests, Vaccines and Treatments

Americans sheltering at home to help “flatten the curve”  might be tempted to buy/use fraudulent products to help diagnose, treat, cure, and even prevent COVID-19

  • Vaccine and drug manufacturers  are working to develop new vaccines and treatments as quickly as possible
  • However, some companies are attempting to profit from pandemic by selling unproven and illegally marketed products that make false claims, such as being effective against the coronavirus

There Are No Vaccines or Medicines for COVID-19, Yet

Protect Yourself and Your Family From Coronavirus Fraud


Image credit: FDA

COVID-19 FDA Guidances


COVID-19-Related FDA Guidance Documents

  • Providing timely recommendations, regulatory information, guidance, and technical assistance necessary to support rapid response efforts
  • Anticipates to immediately implement  guidances
  • Will consider comments received and update as appropriate

Current List includes:

  • Manufacture of Alcohol for Alcohol-Based Hand Sanitizer Products
  • REMS Requirements
  • Ventilators and Accessories and Other Respiratory Devices
  • Non-Invasive Remote Monitoring Devices Used to Support Patient Monitoring
  •  Preparation of Certain Alcohol-Based Hand Sanitizer Products
  • Postmarketing Adverse Event Reporting
  • Conduct of Clinical Trials of Medical Products
  • Food Supplier Verification Onsite Audit Requirements
  • Diagnostic Tests
  • Temporary Compounding of Certain Alcohol-Based Hand Sanitizer Products



COVID-19 Emergency Use Authorizations, Diagnostic Testing policy, N95 Respirators and Surgical Masks


COVID-19 Emergency Use Authorizations (EUA) for Medical Devices and Diagnostics

EUA being granted as there is significant potential for public health emergency that can affect national security or the health and security 

  1. Personal Protective equipment
  2. Diagnostic tests

Personal Protective Equipment


  • Disposable filtering facepiece respirators (FFRs) approved by the National Institute for Occupational Safety and Health (NIOSH)
  • FFRs that were NIOSH-approved but have since passed the manufacturers’ recommended shelf-life, for use in healthcare settings by healthcare personnel (HCP) to prevent wearer exposure to pathogenic biological airborne particulates

Diagnostic Tests


  • Qualitative Real-Time RT-PCR test for qualitative detection of nucleic acid from SARS-CoV-2 in upper and lower respiratory specimens from individuals suspected of COVID-19 by their healthcare provider
  • Positive test result  indicates RNA detected, patient is infected and presumed to be contagious; patient management should follow current CDC guidelines
  • Negative test result means RNA was not present in specimen; does not rule out COVID-19 and should not be used as the sole basis for treatment or patient management decisions




Policy for Diagnostic Tests for COVID-19 during the Public Health Emergency 

Two policies for accelerating the development of certain laboratory tests for COVID-19

  1. EUA submission to FDA
  2. No EUA submission
    • When test is developed under State authorities and State takes responsibility for testing by laboratories
    • CLIA certified and meet requirements

Laboratories offering testing under Policy

  • AdventHealth
  • ARUP Laboratories
  • Assurance Scientific
  • Baylor Scott and White Medical Center – Temple
  • BioReference Laboratories
  • The Children’s Hospital of Philadelphia
  • Diatherix Eurofins
  • Emory Medical Laboratory, Emory Healthcare
  • Gravity Diagnostics
  • Henry Ford Health System
  • HMH Hackensack University Medical Center
  • Hospital of the University of Pennsylvania
  • Houston Methodist Hospital
  • Integrity Laboratories
  • Johns Hopkins Medical Microbiology Laboratory at Johns Hopkins Hospital
  • Montefiore Medical Center
  • New York Presbyterian Hospital -Weill Cornell Medicine (NYPH-WCM)
  • Next Bio-Research Services LLC
  • NYU Langone Medical Center
  • Quest Diagnostics Infectious Disease, Inc.
  • Stanford Health Care Clinical Laboratory
  • Texas Children’s Hospital Department of Pathology
  • TGen North, Clinical Laboratory
  • UCSF-Health
  • University of Washington
  • Viracor Eurofins Clinical Diagnostics

Other FAQs


N95 Respirators and Surgical Masks (Face Masks)

FDA regulates surgical masks and surgical N95 respirators differently based on their intended use

  • Surgical mask : Loose-fitting, disposable device that creates physical barrier between mouth and nose of wearer and potential contaminants in the immediate environment. Edges of mask are not designed to form seal around nose and mouth
  • N95 respirator: Respiratory protective device designed to achieve very close facial fit and very efficient filtration of airborne particles; edges designed to form seal around the nose and mouth.

N95 Respirators not for public use 


Image credit: FDA, CDC

Increased availability of NIOSH approved respirators to healthcare personnel


FDA and CDC take action to increase access to respirators, including N95s, for health care personnel

FDA-CDC collaboration to prioritize access to needed medical products through Emergency Use Authorization (EUA) 

  • Certain industrial respirators during the COVID-19 outbreak in health care settings
  • Respirators approved by NIOSH, but not currently meeting the FDA’s requirements, that may be effective in preventing health care personnel from airborne COVID-19 exposure

EUA does NOT apply to the general American public

  • Should not wear these respirators to protect against COVID-19
  • No added health benefit

FDA information

CDC information

Image credit: FDA

COVID-19 News: New expedited diagnostic testing policy, New York SARS-CoV-2 diagnostic authorization, Medical product shortages, Misinformation about natural products


Policy for COVID-19 Diagnostics Testing in Laboratories Certified to Perform High Complexity Testing under CLIA prior to Emergency Use Authorization 

Policy for novel COVID-19 molecular diagnostics tests developed and used in CLIA laboratories prior to FDA issuance of emergency use authorizations (EUA) 

  • Public health emergency circumstances requiring rapid diagnostic testing to control emergence
  • Rapid COVID-19 detection with accelerated policy enabling CLIA laboratories for more rapid testing capacity
  • Immediately in Effect guidance
  • Accelerated Emergency Use Authorization Template



New York SARS-CoV-2 Realtime Reverse Transcriptase (RT)-PCR Diagnostic Panel 

Wadsworth Center, New York State Department of Public Health 

INDICATION: Presumptive qualitative detection of nucleic acid from SARS-CoV-2 in  nasopharyngeal/oropharyngeal swabs and sputa collected from individuals who meet CDC COVID-19 clinical and/or epidemiological criteria


  • Human Specimen Control (HSC): A human cell culture preparation used as an extraction control and positive control for the RNase P primer and probe set that is extracted and tested concurrently with each specimen extraction run
  • SARS-CoV-2 Positive Control (SARS-CoV-2 Pos): Run with each batch of specimens. Monitors improper assay setup, reagent failures of rRT-PCR reagents and reaction conditions
  • No Template Control (NTC): Nuclease-free water included in each run. Monitors for reagent and system contamination
  • RNase P (RP) control in clinical samples: The RP primer and probe set is included in each run to test for human RNase P, which controls for specimen quality and demonstrates that nucleic acid was generated by the extraction process

REGULATORY PATHWAY: Emergency Use Authorization

  • SARS-CoV-2 can cause a serious or life-threatening disease or condition
  • Based on the totality of scientific evidence, reasonable to believe diagnostic panel may be effective in diagnosing COVID-19
  • There is no adequate, approved, and available alternative

Letter of Authorization

Fact Sheet


COVID-19 Supply Chain Update

Outbreak would likely impact the medical product supply chain, including potential disruptions to supply or shortages of critical medical products in the U.S

  • Alert from a manufacturer about drug shortage due to disruption in China manufacturing
  • In contact with >180 manufacturers of human drugs
  • In contact with 63 manufacturers of essential medical devices
  • Preparing for increasing demand in personal protective equipment—surgical gowns, gloves, masks, respirator protective devices etc
  • Not aware of any cellular or gene therapies that are made in China
  •  No reports of transmission by food or food packaging

Proposals  to prevent or mitigate medical product shortages

  • Lengthen expiration dates
  • Require risk management plans
  • Improve data sharing and require more accurate supply chain information
  • Establish reporting requirements for device manufacturers




Image credits: FDA, NIH

Clinical Trial of Remdesivir to Treat COVID-19


NIH (NIAID) Clinical Trial of Remdesivir to Treat COVID-19 Begins

Randomized, controlled clinical trial to evaluate the safety and efficacy of the investigational antiviral REMDESIVIR in hospitalized adults diagnosed with COVID-19 

  • Remdesivir is an investigational broad-spectrum antiviral treatment with previous testing for treatment for Eboila, MERS and SARS
  • Enrolling hospitalized adults with COVID-19 in Nebraska, Remdesivir vs placebo
  • Participants must have laboratory-confirmed SARS-CoV-2 infection and evidence of lung involvement with need for supplemental oxygen, abnormal chest X-rays, requiring mechanical ventilation
  • Will compare (vs. placebo) participant outcomes on day 15  on seven-point scale (fully recovered – death)


Image credit: FDA and NIAID

News & Views: COVID-19 updates, Rare Disease efforts, Fraudulent DTC genetic tests & review, Stopping illicit medical products from India, Updated Insulin regulatory pathway, Directory for approved drugs (since 1985)


FDA’s Actions in Response to 2019 Novel Coronavirus at Home and Abroad

Active partner in Novel Coronavirus (COVID-19) response, working closely with  Department of Health and Human Services, as well as with international counterparts

  • Active Supply Chain Surveillance: Closely monitor domestic and global supply chain
  • Inspections and Monitoring Compliance of FDA Products Manufactured Overseas: Risk-based surveillance testing of imported products, including those from China
  • Safety of Consumer Products: Close monitoring of fraudulent products and false product claims related to COVID-19
  • Efforts to Diagnose, Treat and Prevent: Expedite development and availability of medical products needed to diagnose, treat and prevent disease
  • Next Steps: Collaborating with interagency partners, international partners, medical product developers and manufacturers to help advance response efforts combat this virus



Rare Disease Day 2020: FDA Continues Important Work on Treatments for Rare Diseases

Commemorating  Rare Disease Day by efforts to get treatments to patients with rare diseases across the thousands of identified rare diseases

  • Public meeting with stakeholders to address challenges and opportunities surrounding rare disease product development
  • New request for applications (RFA) for the Orphan Products Grants Program
  • Additional information on orphan “exclusivity protected uses.”
  • Enhanced rare disease patient website




Collaborative Review of Scientific Evidence to Support Associations Between Genetic Information and Specific Medications

Concerns with DTC genetic tests making claims about genetic test results to manage medication treatment that are NOT supported FDA-approved drug labeling or other scientific evidence

  • Steps to help ensure that claims are grounded in sound science to avoid inappropriate management of patients’ medications
  •  New web-based resource including table describing some of the gene-drug interactions for altered drug metabolism, differential therapeutic effects, differences in risks of adverse events
  • Continue to review various professional guidelines e.g. Clinical Pharmacogenetics Implementation Consortium
  • Continue participation in community-based collaborative approach for ongoing evaluation of the evolving science

Table of Pharmacogenetic AssociationsREAD


FDA Takes Action with Indian Government to Protect Consumers From Illicit Medical Products

Operation Broadsword targeted packages entering the U.S. through International Mail Facility from Jan. 28 through Jan. 30

  • Investigators from both governments examined > 800 shipments, ~50 different FDA-regulated products, many transshipped through third-party countries to conceal point of origin and avoid detection
  • Stopped approximately 500 shipments of illicit, and potentially dangerous, unapproved prescription drugs and combination medical devices from reaching American consumers
  • FDA provided consumer information :  BeSafeRx: Know Your Online Pharmacy.  and encouraged to report any unlawful sale of medical products online to FDA.



Smooth Regulatory Transition of Insulin and Other Biological Products  to Increase Patient Access and Potentially Lower Prices on Insulin

Steps to ensure a smooth transition to new regulatory pathway

  • Final Rule for Biosimilars Action Plan
  • Incorporates changes made by the Biologics Price Competition and Innovation Act of 2009 (BPCI Act) and the Further Consolidated Appropriations Act, 2020
  • Intended to balance innovation and competition and facilitate the development and approval of biosimilar and interchangeable product




Compilation of CDER New Molecular Entity (NME) Drug and New Biologic Approvals

New resource to assist external and agency researchers collecting historical information about FDA’s drug approvals 

  • Provide researchers with curated data regarding drug products approved by CDER since 1985 through 2019
  • Facilitate data accessibility, transparency, and accuracy when researchers seek information about an approved drug
  • Derived from FDA internal databases and document records, and reflects the state of each application at the time of initial regulatory approval
  • CDER will manage the compilation and will update it periodically with the latest drug approval data

Compilation of CDER NME and New Biologic Approvals 1985-2019

Compilation of CDER New Molecular Entity (NME) Drug and New Biologic Approvals – Data Dictionary

Image credit: FDA

Potential Nitrosamines in Medication


What to Know and Do About Possible Nitrosamines in Medication

Ongoing investigation of several potentially cancer-causing substances, called nitrosamines, recently found in blood pressure, heartburn, acid reflux medications

  •  Some drugs – including angiotensin II receptor blockers (ARBs), ranitidine, and nizatidine – have been recalled because of nitrosamine impurities
  • Patients need to talk to their health care professional, as risks of stopping medicine may outweigh the potential risk of exposure to nitrosamines
  • Nitrosamines not expected to cause harm when ingested at low levels


Image credit: FDA

Market Authorizations: 2019-nCoV diagnostic, ERVEBO Ebola vaccine, TEPEZZA for thyroid eye disease

Capture2019-nCoV Real-Time RT-PCR Diagnostic Panel


INTENDED USE: For the presumptive qualitative detection of nucleic acid from the 2019-nCoV in upper and lower respiratory specimens (such as nasopharyngeal or oropharyngeal swabs, sputum, lower respiratory tract aspirates, bronchoalveolar lavage, and nasopharyngeal wash/aspirate or nasal aspirate) collected from individuals who meet CDC criteria for 2019-nCoV testing. Testing is limited to qualified laboratories
designated by CDC and, in the United States, certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), to perform high complexity tests.




  • Reverse transcriptase polymerase chain reaction (PCR) test that provides presumptive detection of 2019-nCoV from respiratory secretions, such as nasal or oral swabs
  • Positive test result indicates likely infection with 2019-nCoV and infected patients should work with their health care provider to manage their symptoms and determine how to best protect the people around them
  • Negative results do not preclude 2019-nCoV infection and should not be used as the sole basis for treatment or other patient management decisions; negative results must be combined with clinical observations, patient history and epidemiological information

REGULATORY PATHWAY: Emergency Use Authorization to address public health  emergency



ERVEBO ebola vaccine for intramuscular injection


INDICATION: Prevention of disease caused by Zaire ebolavirus in individuals 18
years of age and older

ADDRESSING UNMET NEED: First FDA-approved vaccine for the prevention of Ebola virus disease (EVD), caused by Zaire ebolavirus

MECHANISM OF ACTION: Immunization results in an immune response and protection from disease caused by Zaire ebolavirus


  • Guinea study, during 2014-2016 outbreak, n= 3,537 contacts and contacts of contacts with laboratory-confirmed EVD, “immediate” or 21-day “delayed” vaccination
  • ERVEBO 100% effective in preventing Ebola cases with symptom onset greater than 10 days after vaccination
  • No EVD cases in “immediate” cluster group vs 10 cases in 21-day “delayed” cluster group
  • Liberia study- n= 477, Sierra Leone study – n=500, Canada, Spain, US study – n=900
  • Antibody responses in Canada, Spain and U.S. study were similar to those among individuals in the studies conducted in Liberia and Sierra Leone.


  • Most commonly reported side effects were pain, swelling and redness at the injection site, as well as headache, fever, joint and muscle aches and fatigue.


  • Priority Review and Tropical Disease Priority Review Voucher, Breakthrough Therapy designation
  •  Because of public health importance, FDA worked closely with Merck and completed its BLA evaluation in less than six months



TEPEZZA (teprotumumab-trbw) injection, for intravenous use

Horizon Therapeutics

INDICATION: Treatment of Thyroid Eye Disease


  • First drug approved for the treatment of thyroid eye disease-
  • Rare condition where muscles and fatty tissues behind eye become inflamed, causing eyes to be pushed forward and bulge outwards (proptosis)

MECHANISM OF ACTION: Not been fully characterized- binds to IGF-1R and blocks  activation and signaling


  • Two studies, n=170 patients with active thyroid eye disease, TEPEZZA or placebo
  • Primary endpoint: >2 millimeter reduction in proptosis- 71% (Study 1) and 83% (Study 2) vs. 20% and 10%


  • Most common adverse reactions: Muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing loss, dry skin, dysgeusia, headache
  • Should not be used if pregnant, counseling on pregnancy prevention during treatment and for 6 months following last dose


  • Priority Review, in addition to Fast Track and Breakthrough Therapy Designation 
  • Orphan Drug designation, with support from FDA Orphan Products Grants Program
  • Postmarketing commitments: Additional studies to characterize efficacy, safety, quality


Image credits: FDA, Merck, Horizon Therapeutics








News and Views: Coronavirus medical countermeasures, 2019 New Therapies, Gene Therapy innovation, Deter anti-competitive business for biologics, Heart Health education for women, HIV Drugs mobile database, Warning for nicotine toothpicks


Advance Development of Novel Coronavirus Medical Countermeasures (MCM)

FDA collaborating with interagency partners, product developers, international partners and global regulators to
  • Expedite development and availability of MCM to diagnose, treat, mitigate, prevent
  • Utilize pathways, including Emergency Use Authorization (EUA) to more rapidly make MCM available
  • Provide regulatory advice, guidance, and technical assistance to  sponsors developing investigational MCMs
  • Provide review and feedback on development proposals including design and set-up of clinical trials
  • Protect safety of nation’s blood supply and human cells, tissues,cellular/tissue-based products for transplantation
  • Enable access to investigational MCM through EUA or expanded access mechanisms
  • Protect consumers against fraudulent products by monitoring fraudulent products and false product claims and taking appropriate action

READ , 2019-nCOV website 


2019 CDER New Drug Approvals Report

Annual report entitled Advancing Health Through Innovation: New Drug Therapy Approvals

  • Variety of novel drugs for advancing patient care – never approved in US
  • Overview of other notable approvals — new uses of uses for approved drugs
  • Treat new population of patients, such as children
  • Innovative ways to enhance efficiency and expedite review and approval

Innovation and Access areas

  • Rare Diseases
  • Neurological and Psychiatric disorder
  • Infectious diseases
  • Heart, Lung, Circulatory, Endocrine diseases
  • Autoimmune conditions
  • Women’s and Men’s specific health issues
  • Cancers and blood disorders
  • Biosimilars



Strong Support of Innovation in Development of Gene Therapy Products

FDA efforts  to support innovators developing new gene therapy products, which insert new genetic material into a patient’s cells

  • 4 products approved
  • > 900 investigational new drug (IND) applications for ongoing clinical studies
  • will serve to improve therapeutic choices

Publication of guidances issued to provide recommendations for product developers



New Efforts to Further Deter Anti-Competitive Business Practices, Support Competitive Market for Biological Products to Help Americans

FDA and FTC to collaborate to curtail and discourage anti-competitive behavior to faciliate robust competition and bring down cost for biologics

  1. Promote greater competition in biologic markets
  2. Deter behavior that impedes access to samples needed for the development of biologics, including biosimilars
  3. Take appropriate action against false or misleading communications
  4. Review patent settlement agreements involving biologics, including biosimilars, for antitrust violations


CaptureHeart Health Education for Women

FDA Office of Women’s Heath (OWH) initiatives is support of American Heart Month
  • Heart health educational video ‘Getting a Beat : On what women know about heart health
  • New KNOWH the Difference initiative, which focuses on sharing important knowledge and news on women’s health (KNOWH)
  • OWH research and extramural funding opportunities

Mobile-Friendly Database with Information on Life-Saving HIV Drugs

Interactive database  on critical information about antiretrovirals (ARVs) eligible for purchase under the President’s Emergency Plan for AIDS Relief (PEPFAR) program

  • Empower public and health care providers by enhancing the amount and availability of information and data provided on each drug
  • Health care providers, consumers, procurer access to FDA-reviewed product labeling and essential scientific information for safe and effective use of drug
  • Information on pediatric drugs, where manufactured, shelf-life, storage requirements
  • Ability to export reports, collect metrics, readily access on mobile platforms


FDA Warns Maker of Nicotine-Containing Toothpicks of Several Violations, Including Illegal Sales 

  • Warning letter to Smart Toothpicks LLC,  Tempe, Arizona, for selling dissolvable tobacco products, including Peppermint Ice Nicotine Toothpicks
  • Three specific violations:
    • selling a tobacco product to a minor through the company’s website
    • selling unauthorized modified risk tobacco products
    • failing to include required nicotine warning statements on both packaging and advertising
  • Written response to this letter within 15 working days on corrective actions
    • discontinue violative labeling, advertising, sale, and/or distribution
    • plan for maintaining compliance with the FD&C Act

Action is part of the agency’s Youth Tobacco Prevention Plan, to prevent and reduce youth tobacco use 


Image credits: FDA

e-cigarettes: Enforcement policy on unauthorized flavored cartridges


Enforcement policy on unauthorized flavored cartridge-based e-cigarettes that appeal to children, including fruit and mint

FDA intends to prioritize enforcement against these illegally marketed ENDS products by focusing on the following groups of products that do not have premarket authorization

  • Any flavored, cartridge-based ENDS product (other than a tobacco- or menthol-flavored ENDS product)
  • All other ENDS products for which the manufacturer has failed to take (or is failing to take) adequate measures to prevent minors’ access
  • Any ENDS product that is targeted to minors or likely to promote use of ENDS by minors.

Companies that do not cease manufacture, distribution and sale of unauthorized flavored cartridge-based e-cigarettes (other than tobacco or menthol) within 30 days risk FDA enforcement actions


Image credit: FDA

Device Authorizations: COBAS MRSA diagnostic, WOUNDCHECK for bacterial status, GSP Neonatal Creatine Kinase for Duchenne, CONTROL-IQ for diabetes

CaptureCOBAS vivoDx MRSA diagnostic test 

Roche Molecular Systems Inc.

INDICATION FOR USE: Automated qualitative in vitro diagnostic test for the direct detection of live methicillin-resistant Staphylococcus aureus (MRSA) cells in nasal swab samples from patients who are at risk for nasal colonization by MRSA.
The test utilizes selective agents and bioparticles (Smarticles technology) to introduce a luciferase gene into targeted bacteria to create an amplified luminescent signal in only viable (live) MRSA cells. The cobas vivoDx MRSA test is intended to aid in the prevention and control of MRSA infections in healthcare settings. It is not intended to diagnose MRSA infections, nor to guide, or monitor treatment. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

ADDRESSING UNMET NEED: New tool in the fight to prevent and control MRSA in high-risk settings

DESCRIPTION: System for detection of microorganisms and antimicrobial resistance using reporter expression

  • New bacteriophage technology based on bioluminescence to detect MRSA from nasal swab samples in 5 hours vs  compared to 24-48 hours for conventional culture

PERFORMANCE TESTING: Test correctly identified MRSA in  90% of samples where MRSA was present and 98.6% of samples with no MRSA

RISKS: Failure to use the device correctly, False positive or negative results, Failure to interpret results correctly

MITIGATIONS: Labeling, Design verification and validation, Other special controls

REGULATORY PATHWAY: De Novo premarket review pathway



WOUNDCHEK Bacterial Status

Woundcheck Laboratories

INDICATION FOR USE: in vitro diagnostic chromatographic test for qualitative detection of bacterial protease activity directly from wound fluid samples collected with a swab. The WCBS test is intended for use in adult patients as an aid in assessing the risk for nonhealing of chronic venous, diabetic foot, and pressure ulcers associated with wounds where there are no signs of wound infection and where patients are asymptomatic for clinical signs of infection. The test is intended for use with chronic wounds that are between 21 days and < 6 months of age and chronic wounds that are ≥ 6 months of age that are < 1cm2 in size.

DEVICE TYPE: To detect bacterial protease activity in chronic wound fluid

  • Lateral flow prescription device that may include a sterile swab
  • Intended for use in patients as an aid in assessing the risk for non-healing of chronic venous, diabetic foot, and pressure ulcers associated with wounds where there are no signs of wound infection and where patients are asymptomatic for clinical signs of infection.

RISKS: Failure to use the device correctly, False positive or negative results, Failure to interpret results correctly

MITIGATIONS: Labeling, Design verification and validation, Other special controls

REGULATORY PATHWAY: De Novo premarket review pathway



GSP Neonatal Creatine Kinase – MM kit


ADDRESSING UNMET NEED: First test to aid in newborn screening for Duchenne Muscular Dystrophy (DMD), a rare genetic disorder that causes progressive muscle deterioration and weakness

DESCRIPTION: Muscular dystrophy newborn screening test

  • Intended to measure creatine kinase levels obtained from dried blood spot specimens on filter paper from newborns (prick of a newborn’s heel 24 to 48 hours after birth) as an aid in screening newborns for muscular dystrophy
  • Kit works by measuring the concentration of a type of protein called CK-MM, which is part of a group of proteins called creatine kinase
  • Creatine kinase is found in muscle tissue and CK-MM enters the blood stream in increased amounts when there is muscle damage


  • Clinical study, n=3,041 newborns, dried blood samples tested for DMD associated protein levels
  • Kit able to accurately identify the four screened newborns that had DMD-causing genetic mutations
  • Additional testing of 30 samples from newborns with clinically confirmed cases of DMD; all correctly identified

RISKS: False positive and False negative results

MITIGATIONS: Labeling, Design verification and validation, Special controls

REGULATORY PATHWAY: De Novo premarket review pathway


CaptureControl-IQ Technology

Tandem Diabetes Care

INDICATION FOR USE: Intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps to automatically increase, decrease, and suspend delivery of basal insulin based on iCGM readings and predicted glucose values. It can also deliver correction boluses when the glucose value is predicted to exceed a predefined threshold.
Control-IQ technology is intended for the management of Type 1 diabetes mellitus in persons 14 years of age and greater.
Control-IQ technology is intended for single patient use and requires a prescription.
Control-IQ technology is indicated for use with NovoLog or Humalog U-100 insulin.

DESCRIPTION: Interoperable automated glycemic controller

  • Intended to automatically calculate drug doses based on inputs such as glucose and other relevant physiological parameters, and to command the delivery of such drug doses from a connected infusion pump
  • Designed to reliably and securely communicate with digitally connected devices to allow drug delivery commands to be sent, received, executed, and confirmed. Interoperable automated glycemic controllers are intended to be used in
    conjunction with digitally connected devices for the purpose of maintaining glycemic control.


  • Inability of the controller to handle different pharmacokinetic and pharmacodynamic characteristics of the drugs
  • Lack of compatibility of connected devices
  • Connected devices having inadequate performance to allow safe use of  controller
  • Failure to report device malfunctions or adverse events to manufacturer
  • Latent flaws in software
  • Failure to provide appropriate treatment due to loss of communication with
    connected devices
  • Risk due to insecure transmission of data
  • Failure to correctly determine the root cause of device malfunctions
  • Data transmission interference/electromagnetic disturbance

MITIGATIONS: Device performance, drug compatibility information in labeling
User training, Validation of processes, and procedures as well as limitations with connected and interoperable devices, Assigning post-market responsibilities. Software validation testing, Electrical safety verification and validation, electromagnetic compatibility,radio frequency wireless testing, user training

REGULATORY PATHWAY: De Novo premarket review pathway


Image credits:  Roche, Woundcheck Labs, PerkinElmer, Tandem

News & Views: 24th FDA Commissioner, Drug importation from Canada, Center of Excellence for drug compounding, Acute pain opioid prescribing, Generic drug pricing, Operation Vapor Lock, Naloxone and opioid overdose, 2019-2020 Flu season



Stephen Hahn, MD, confirmed as the 24th FDA Commissioner

  • Radiation Oncologist with Residency at the National Cancer Institute
  • Professor at University of Pennsylvania
  • Chief Medical Executive at MD Anderson Cancer Center


Steps to lower U.S. prescription drug prices

Allow importation of certain prescription drugs shipped from Canada

  • Purpose of proposed rule is to lower prices and reduce out of pocket costs
  • Foreign seller, licensed by Health Canada and registered with FDA, to purchase directly from manufacturer
  • US importer, subject to the supply chain security requirements, to buy directly from foreign seller
  • Importer arranges for statutorily prescribed testing for authenticity, degradation, and other requirements by a qualifying US laboratory
  • Post-importation requirements including adverse event, medication error, field alert to manufacturer and to FDA


CaptureImproving quality of compounded drugs

Novel approaches to reduce risks with production practices of outsourcing facilities 

  • Establishing Compounding Quality Center of Excellence to enhance collaboration among and provide educational programs for outsourcing facilities
  • Three main areas of focus: in-person, online education and trainings, conference to exchange ideas and best practices, market research help inform FDA on key issues


Capture.JPGCapture.JPGNational Academies of Sciences, Engineering, and Medicine (NASEM) report on framing opioid prescribing guidelines for acute pain

FDA contracted NASEM for evidence-based guidelines for opioid analgesic prescribing for acute pain. NASEM recommendations are:

  • Develop an analytic framework (e.g., Figure above ) to develop and assess evidence base for clinical practice guidelines (CPG)
  • Outpatient opioid prescribing CPGs should explicitly state patient populations  (e.g., adults versus children) and contextual aspects (e.g. setting, prescriber type, prior treatments)
  • To determine optimal opioid prescribing strategies, examine not only intermediate outcomes (e.g. pills prescribed, unused, long-term opioid use), but also the short- and long-term health outcomes (e.g. mortality, overdose, opioid use disorder, pain, and function)
  • Well-designed observational and quality improvement initiatives helpful for evaluating the effects of opioid prescribing strategies on health outcomes
  • CPGs should be implemented by governmental (federal, state, and local) and nongovernmental entities
  • Prioritized surgical and medical indications listed for CPG development
  • State the role of opioid alternatives as first-line therapies, specify any other interventions, including nonopioid interventions, used to relieve pain


Capture.JPGGreater Generic Competition and Lower Generic Drug Prices

  • New analysis showing greater competition among generic drug makers associated with lower generic drug prices
  • With six or more competitors,  price reductions of >95% compared to brand prices before generic entry
  • FDA helping bring greater efficiency and transparency to generic drug review process to encourage competition


Capture.JPGOperation Vapor Lock seized sale of  illicit THC vaping cartridges 

FDA and DEA have seized 44 websites advertising the sale of illicit THC vaping cartridges 

  • Website advertising under various brand names with information indicating sale items would be considered a controlled substance under federal law
  • Some websites solely to fraudulently obtain payments without intending to mail product


Capture.JPGHaving Naloxone on Hand Can Save a Life During an Opioid Overdose

Naloxone is a life-saving drug that, when sprayed into the nose or injected, quickly reverses the powerful effects of opioids during an overdose

  • Expanded availability by allowing consumers to get directly from pharmacist, by putting a “standing order”
  • Need to recognize opioid overdose and use Naloxone
  • Will not harm if no opioids in system
  • Discuss Naloxone when getting opioid prescription


Capture.JPG2019-2020 Influenza season

Flu vaccine lots that have been released by FDA and are available for distribution by the manufacturers


Image credit: FDA

Medicines and Driving


Some Medicines and Driving don’t Mix

  • Some prescription and nonprescription medicines have side effects and cause reactions that may make it unsafe to drive (e.g.opioid pain relievers, anti-anxiety, anti-seizure drugs, antipsychotic, antidepressants, codeine)
  • Cannabidiol (CBD) products and driving can be dangerous
  • Some sleep medicines can impair even the next morning
  • Allergy medicines can affect ability to drive


Image credit: FDA

Drug Authorizations: OXBRYTA and ADAKVEO for sickle cell, XCOPRI for partial-onset seizures, CALQUENCE for leukemia/lymphoma, GIVLAARI for acute hepatic porphyria


OXBRYTA (voxelotor) tablets

Global Blood Therapeutics

INDICATION FOR USE: Treatment of sickle cell disease (SCD) in adults and pediatric patients 12 years of age and older.

ADDRESSING UNMET NEED: Treatment option for 100,000 people in the U.S., and the more than 20 million globally, who live with this debilitating blood disorder

MECHANISM OF ACTION: Hemoglobin S (HbS) polymerization inhibitor that binds to HbS with a 1:1 stoichiometry and exhibits preferential partitioning to red blood cells (RBCs) – increasing the affinity of Hb for oxygen


  • Randomized, double-blind, placebo-controlled, multicenter trial, n=274 patients with sickle cell disease, OXBRYTA vs. placebo
  • Endpoint: Hb response rate defined as a Hb increase of >1 g/dL from baseline to Week 24
  • 51.1% (OXBRYTA) vs. 6.5% (placebo),  (p < 0.001); no outlier subgroups observed


  • Common side effects: Headache, diarrhea, abdominal pain, nausea, fatigue, rash and pyrexia


  •  Accelerated Approval, Fast Track designation. Orphan Drug designation
  • Accelerated approval requirements: Phase 3, randomized, doubleblind, placebo-controlled trial in pediatric patients (age 2 years to < 15 years) with Sickle Cell Disease , long-term (5 years) followup



ADAKVEO (crizanlizumab-tmca) injection


INDICATION FOR USE: Reduce the frequency of vasoocclusive crises (VOCs) in adults and pediatric patients aged 16 years and older with sickle cell disease.

ADDRESSING UNMET NEED: First targeted therapy approved for sickle cell disease, specifically inhibiting selectin, a substance that contributes to cells sticking together and leads to vaso-occlusive crisis- a painful condition

MECHANISM OF ACTION: Humanized IgG2 kappa monoclonal antibody that binds to P-selectin and blocks interactions between endothelial cells, platelets, red blood cells, and leukocytes.


  • 52-week, randomized, multicenter, placebo-controlled, double-blind study, n=198 patients with sickle cell disease, any genotype, ADAKVEO vs placebo
  • Endpoint: Annual rate of vaso-occlusive crisis (VOC) to a healthcare visit
  • Median annual rate of 1.63 visits (ADAKVEO) vs. 2.98 visits (placebo)
  • 36%  on Adakveo did not experience VOC during the study, delayed the time of first VOC experience


  • Common side effects: Back pain, nausea, pyrexia, arthralgia
  • Need to monitor patients for infusion-related reactions,  interference with automated platelet counts or platelet clumping


  •  Priority Review and Breakthrough Therapy designation, Orphan Drug designation
  • Postapproval requirements: Further evaluation of immune mediated safety



XCOPRI® (cenobamate tablets)

SK Lifesciences

INDICATION FOR USE: Treatment of partial-onset seizures in adult patients

ADDRESSING UNMET NEED: New option to treat adults with partial-onset seizures, which is an often difficult-to-control condition that can have a significant impact on patient quality of life

MECHANISM OF ACTION: Precise mechanism unknown; demonstrated to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents


  • Two multicenter, randomized, double-blind, placebo-controlled studies, N=655 adult patients
  • Endpoint: % change from baseline in seizure frequency per 28 days in the treatment period
  • 55.6%  reduction (XCOPRI 200 mg) vs 21.5% reduction (placebo), p< 0.0001


  • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS),  shortening of the QT interval and ventricular fibrillation – dose needs to be titrated
  • Increased risk of suicidal thoughts or behavior and other neurological adverse reactions
  • Most common side effects: Somnolence (sleepiness), dizziness, fatigue, diplopia (double vision), headaches


  • Contains cenobamate – (Controlled substance schedule to be determined after review by the Drug Enforcement Administration
  • Required pediatric assessments


CaptureCapture.JPGCALQUENCE® (acalabrutinib) capsules


INDICATION FOR USE: treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)


  • Two randomized, actively controlled trials in patients with CLL
  • Endpoint:  Progression-free survival (PFS) as assessed by independent review; significantly improved in both acalabrutinib arms, p<0.0001
  • Most common adverse reactions: Anemia, neutropenia, thrombocytopenia, headache, upper respiratory tract infection, diarrhea


  • First approved in 2017 
  • This review conducted under Project Orbis, framework for concurrent submission and review by FDA, the Australian Therapeutic Goods Administration, and Health Canada
  • FDA review used the Real-Time Oncology Review (RTOR) and Assessment Aid pilot programs, to sreamline data submission, Priority Review and Breakthrough Therapy designation


CaptureGIVLAARI (givosiran) injection

Alnylam Pharmaceuticals

INDICATION FOR USE: Treatment of adults with acute hepatic porphyria (AHP)

MECHANISM OF ACTION: Double-stranded small interfering RNA that causes degradation of aminolevulinate synthase 1 (ALAS1) mRNA in hepatocytes;  leads to reduced circulating levels of neurotoxic intermediates aminolevulinic acid
(ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of AHP


  • Randomized, double‑blind, placebo‑controlled, multinational trial, n=94 patients with AHP, GIVLAARI vs placebo
  • Endpoint: Rate of porphyria attacks requiring hospitalizations, urgent healthcare visit, or intravenous hemin administration at home
  • 1.9 (95% CI:1.3,2.8) with GIVLAARI vs, 6.5 (95% CI:4.5, 9.3) with placebo
  • 70% (95% CI: 60%, 80%) fewer porphyria attacks with GIVLAARI


  • Most common adverse reactions: Nausea and injection site reactions
  • Warnings for anaphylactic reactions, hepatic and renal toxicities, and injection site reactions


  • Priority Review, Orphan product, Breakthrough Therapy designations
  • Postmarketing commitments: Trial in pediatric patients age greater than or equal to 12 years to less than 17 years with AHP


Image credit: Global Blood Therapeutics, Novartis, SK Lifesciences, AstraZeneca, Alnylam



CURE ID crowdsourcing App for novel uses of existing medicines


 CURE ID app for health care professionals to report novel uses of existing medicines for patients with difficult-to-treat infectious diseases

Allow clinical community to report experiences treating difficult-to-treat infectious diseases with novel uses of existing FDA-approved drugs

  • Focus on infectious diseases lacking adequate treatments, neglected tropical diseases, emerging infectious drug-resistant threats
  • Collects simple case report form from caregivers about experience using an approved product for an unapproved use
  • Organizes and analyzes data fast for promising new uses for existing drugs
  • Collaboration between FDA and the National Center for Advancing Translational Sciences (NCATS), NIH


Image credit: FDA

Device Authorizations: MYRIAD myChoice CDx diagnostic, PENTAX duodenoscope, MISIGHT contact lens, TULA system for otitis media


MYRIAD myChoice® CDx

Myriad Genetic Laboratories, Inc.

INDICATION FOR USE: Next generation sequencing-based in vitro diagnostic test that assesses the qualitative detection and classification of single nucleotide variants, insertions and deletions, and large rearrangement variants in protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes and the determination of genomic Instability Score (GIS) which is an algorithmic measurement of Loss of Heterozygosity (LOH), Telomeric Allelic Imbalance (TAI), and Large-scale State Transitions (LST) using DNA isolated from formalin-fixed p raffin embedded (FFPE) tumor tissue specimens.

The results of the test are used as an aid in identifying ovarian cancer patients with positive homologous recombination deficiency (HRD) status for treatment with the targeted therapy  in accordance with the approved therapeutic product labeling.

ADDRESSING UNMET NEED: First diagnostic for testing of FFPE ovarian tumor tissue for the selection of patients who are eligible for treatment with niraparib (Zejula)


  • Single-site assay; includes reagents, software, instruments and procedures for testing DNA extracted from formalin-fixed, paraffin-embedded (FFPE) tumor samples
  • Employs single DNA extraction method from FFPE specimens, 30-200 ng of which undergoes multiple steps including fragmentation, end repair and adenylation, adapter ligation, library construction/amplification, hybridization and capture, sequencing and data analysis


  • Clinical test as an aid to clinicians in identifying ovarian cancer patients who may be eligible for treatment with Zejula (niraparib)
  • Primary endpoint: Overall Response Rate (ORR), key secondary endpoints were ORR in all patients and Median DOR (duration of response) in all patients
  • In patients with tBRCAm tumors (n=63), ORR was 28.6% and median DOR 9.2 mo.
  • Statistically significant overall response rate with clinically meaningful DOR seen in  patients with deleterious or suspected deleterious BRCA mutation, positive GIS status,  patients who had received prior chemotherapy
  • Overall, the response rate is better than what would be expected of available therapy and represents an improvement in a surrogate endpoint that is reasonably likely to predict clinical benefit
  • Risks are associated with potential mismanagement of patients resulting from false results of the test or a failure to receive results


  • Device Generic Name: Next Gen Sequencing oncology panel, somatic or germline variant detection system
  • Device Procode: PQP

Patient Labeling: Test Request Form

CapturePENTAX Medical Video Duodenoscope ED34-i10T2


INDICATION FOR USE: To provide visualization and access to the upper gastrointestinal (GI) tract to treat bile duct disorders and other upper GI problems

ADDRESSING UNMET NEED: First duodenoscope with disposable elevator piece, reducing the number of parts needing disinfection. Represents a major step toward lowering the risk of infection among patients who undergo procedures with these devices


  • Intended to be used with endoscopic devices, introduced in patient’s mouth
  • Provides visualization via a video monitor of and therapeutic access to the biliary tract (liver, gall bladder and bile ducts) through the upper gastrointestinal tract
  • Risks: Ootential for injuries, including, but not limited to, burns, electric shock, perforation, infection and bleeding


CaptureMISIGHT (omafilcon A) contact lens

Cooper Vision

INDICATION FOR USE: Single use Soft Contact Lenses for the correction of myopic  ametropia and for slowing the progression of myopia in children with non-diseased eyes, who at the initiation of treatment are 8-12 years of age and have a refraction of -0.75  to -4.00 diopters (spherical equivalent) with ≤ 0.75 diopters of astigmatism.

The lens is to be discarded after each removal

ADDRESSING UNMET NEED:  First contact lens indicated to slow the progression of myopia (nearsightedness) in children, which ultimately could mean a reduced risk of developing other eye problems


  • Three-year randomized, controlled clinical trial , n=135 children ages 8 to 12, MiSight vs. conventional soft contact lens
  • Progression in myopia with MiSight lenses less than conventional lenses, less change in the axial length of eyeball at each annual checkup
  • No serious ocular adverse events in either arm of the study
  • Additionally, real world data from a retrospective analysis of n-782 medical records from seven community clinics. Ulcer rate comparable to adults who wear contact lenses daily
  •  Required postmarket study to further evaluate the safety and effectiveness


  • Classification name:  Daily Wear Soft Contact Lens To Reduce The Progression Of Myopia
  • Product Code: QIT


Capture.JPGTULA System

Tusker Medical

INDICATION FOR USE: Tubes Under Local Anesthesia (TULA) System for delivery of tympanostomy tubes, that can be inserted into the eardrum to treat recurrent otitis media.

ADDRESSING UNMET NEED: An option for the treatment of recurrent ear infections that does not require general anesthesia. Has the potential to expand patient access to treatment that can be administered in  physician’s office with local anesthesia and minimal discomfort


  • Consists of an Iontophoresis System, a local anesthetic, and a Tube Delivery System
  • Iontophoresis System is designed to provide child-friendly bilateral local anesthesia of the tympanic membrane, enabling a viable alternative to general anesthesia
  • Once the tympanic membrane is numb, the Tube Delivery System is used to insert the tympanostomy tube
  • With a single button push, the Tube Delivery System automatically creates the myringotomy and inserts the tube in less than 500 milliseconds
  • Parents are present during the TULA office-based procedure, and younger children may sit on their parent’s lap, if desired.


  • Study with 222 pediatric patients to assess the effectiveness of the Tula System for the delivery of ear tubes
  • Procedural success rate was 86% and 89% in children younger than age 5 and between ages 5-12 years old, respectively
  • Most common adverse event: Inadequate anesthesia during the procedure.


  • Breakthrough Device designation

Image Credit:Myriad Genetic Laboratories, Pentax, Cooper Vision, Tusker Medical

News & Views: Cybersecurity, Technology Modernization Action Plan, Implementing SUPPORT Act, Homeopathic products oversight, Breast implants safety, CBD warning for pregnancy, CDRH Patient Engagement, New youth e-cigarette education


Medical Device Cybersecurity : Information for patients

New technologies can be implantable or wearable, used at home or in health care settings: Safer, timelier and more convenient

Anytime a medical device has software and relies on a wireless or wired connection, vigilance is required : Vulnerable to cyber threats and requires cybersecurity

Patients need to

  • Apply software updates
  • Register device with manufacturer
  • Be observant and vigilant
  • Involve  family or caregivers
  • If there is a serious event, seek medical attention.

Capture.JPGFDA’s Technology Modernization Action Plan (TMAP)

Technological foundation for development of FDA’s ongoing strategy around data

  • For stewardship, security, quality control, analysis, and real-time use of data
  • Will accelerate path to better therapeutic and diagnostic options

Proposal to

  • Modernize FDA’s technical infrastructure 
  • Develop technology products to support FDA’s regulatory mission
  • Communicate and collaborate with stakeholders to drive technological progress that is interoperable across the system


Capture.JPGFDA first year accomplishments implementing SUPPORT Act authorities to address the opioids crisis

FDA’s implementation of the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act (SUPPORT Act)

  • Clarifying FDA regulation of non-addictive pain products
  • Evidence-based opioid analgesic prescribing guidelines and report
  • Strengthening FDA and U.S. Customs and Border Protection (CBP) coordination and capacity
  • Restricting entrance of illicit drugs
  • Safety-enhancing packaging and disposal
  • Clarifying FDA postmarket authorities
  • Study on abuse-deterrent opioid formulations access barriers under Medicare


Capture.JPGEfforts to protect patients from potentially harmful drugs sold as homeopathic products

Homeopathic products are marketed without FDA review and may not meet standards for safety, effectiveness, quality and labeling

  • Issuance of draft guidance discussing risk-based enforcement approach to drug products labeled as homeopathic
  •  Withdrawing outdated Compliance Policy Guide (CPG) 400.400, entitled “Conditions Under Which Homeopathic Drugs May be Marketed”

Risk-based approach with appropriate regulatory and enforcement actions when  patients are being put at risk


Capture.JPGEfforts to protect women’s health and enhance safety information available to patients considering breast implants

 Draft guidance  to ensure patients have complete information about the benefits and risks of breast implants

  • Boxed Warning in labeling: Not lifetime devices, chances of developing complications, associated with risk of developing breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)
  • Inclusion of patient decision checklist at end of patient informational booklet
  • Revision of rupture screening recommendations for silicone gel-filled implants
  • Inclusion of product  ingredient information  that is easily understood by patients

To help patients better understand breast implant benefits and risks in making health care decisions that fit patients’ needs and lifestyle 


CaptureWarning against Using Cannabis, Including CBD, When Pregnant or Breastfeeding

FDA strongly advises against use of cannabidiol (CBD), tetrahydrocannabinol (THC), and marijuana in any form during pregnancy or while breastfeeding

Unapproved products and FDA does not know

  • safety and effectiveness to treat a particular disease
  • what, if any, dosage may be considered safe
  • interaction with other drugs or foods
  • whether they have dangerous side effects or other safety concerns


CaptureCDRH Patient Engagement

Mission to engage with patients, understand their perspective, and proactively integrate the patients’ perspectives into the total product life cycle of medical devices 

  • Designing medical devices
  • Planning and conducting medical device clinical investigations
  • Informing CDRH’s thinking on current issues impacting a patient community
  • Helping to identify emerging signals
  • Communicating safety messages
  • Identifying specific populations’ perspectives on benefit-risk for a given treatment

Ways to engage



CaptureWork  with Scholastic with launch of new youth e-cigarette prevention educational resources for middle and high schools

Education is an important complement to the FDA’s overarching youth tobacco prevention efforts

  • Continuing to educate youth, parents, and teachers about the dangers of e-cigarette use
  • Joined forces with Scholastic to develop and distribute educational resources to high school educators across the country
  • Expanding collaboration with Scholastic to include middle school educators
  • Help ensure that > one million middle and high school teachers have resources to start educational conversations about the harms of e-cigarette use with their students


Image credit: FDA

Authorizations: ORAQUICK Ebola test, TRIKAFTA for cystic fibrosis, REYVOW for migraine, SCENESSE for erythropoietic protoporphyria



OraSure Technologies, Inc

INDICATION FOR USE: In vitro diagnostic single-use immunoassay for the qualitative detection of antigens from viruses within the Ebolavirus genus but does not differentiate
between these viruses

ADDRESSING UNMET NEED: First rapid diagnostic test for the Ebola Virus Disease (EVD). The test provides a rapid, presumptive diagnosis that must be confirmed.

TYPE OF DEVICE: Device to detect antigens of biothreat microbial agents in human clinical specimens.

To detect antigens of biothreat microbial agents in human clinical specimens is  identified as an in vitro diagnostic device intended for the detection of antigens of microbial agents in specimens collected from patients with signs and symptoms of infection with biothreat microbial agents and who have been exposed to these agents or are suspected or at risk of exposure. The device can include antibodies for  immobilization and detection of the analyte. This device may also be used for cadaver testing to prevent human diseases for which cadavers constitute a source of human-to-human transmission.


  • Data from multiple clinical studies of blood samples and cadaveric oral fluid from the 2014 West African outbreak and analytical studies
  • Reasonable assurance of the safety and effectiveness when intended to identify antigens associated with Ebola virus in blood from symptomatic patients and oral fluid of cadavers – with high levels of Ebola virus
  • OraQuick Ebola Test is not intended to be used for general Ebola infection screening (e.g., airport screening) or testing of individuals at risk of exposure without observable signs of infection

REG PATHWAY: De Novo classification

  •  Emergency Use Authorization (EUA) pathway -Collaboration between FDA, WHO and Democratic Republic of Congo (DRC)
  • Breakthrough Device designation
  • Regulation Number: 21 CFR 866.4002
  • Regulation Name: Device to detect antigens of biothreat microbial agents in human clinical specimens
  • Regulatory Class: Class II
  • Product Code: QID



 TRIKAFTA (elexacaftor/ivacaftor/tezacaftor) tablet


INDICATION: Treatment of cystic fibrosis (CF) in patients aged 12 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one F508del mutation.

ADDRESSING UNMET NEED: First triple combination therapy available to treat patients with the most common cystic fibrosis mutation.

MECHANISM OF ACTION: Elexacaftor and tezacaftor bind to different sites on the CFTR protein to increase the amount of CFTR protein delivered to the cell surface. Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface. The combined effect of elexacaftor, tezacaftor and ivacaftor is increased quantity and function of F508del-CFTR at the cell surface, resulting in increased CFTR activity


  • 2 randomized, double-blind, active and placebo-controlled trials, patients with CF, 12 years and older
  • First trial – n=403 with F508del mutation and mutation on second allele  that is not responsive to ivacaftor or tezacaftor/ivacaftor alone
  • Second trial- n=107 patients with two identical F508del mutations
  • Primary analysis: Increases in % predicted forced expiratory volume in one second, (ppFEV1). Trikafta increased the ppFEV1 in both trials ( 13.8% from baseline vs.  placebo and 10% from baseline vs. tezacaftor/ivacaftor)


  • Serious adverse drug reactions: Rash and influenza (flu) events
  • Most common adverse drug reactions: Headaches, upper respiratory tract infections, abdominal pains, diarrhea, rashes, increased liver enzymes (alanine aminotransferase and aspartate aminotransferase), nasal congestion, increased blood creatine phosphokinase, rhinorrhea, rhinitis, influenza, sinusitis and increased blood bilirubin
  • Warnings related to elevated liver function tests 


  • Priority Review, Fast Track, Breakthrough Therapy, and orphan drug designation
  • Rare pediatric disease priority review voucher
  • Postmarketing requirements: Rat carcinogenicity studies, hepatic impairment study



REYVOW (lasmiditan)

Eli LIlly

INDICATION: Acute treatment of migraine with or without aura in adults.

ADDRESSING UNMET NEED: New option for the acute treatment of migraine that affects one in seven Americans

MECHANISM OF ACTION: Binds with high affinity to the 5-HT1F receptor; presumably exerts its therapeutic effects ithrough agonist effects at the 5-HT1F receptor


  • 2 randomized, double-blind, placebo-controlled trials, n=3,177 adult patients with history of migraine with and without aura, REYVOW vs, placebo
  • Primary Endpoint: % patients whose pain resolved and whose most bothersome migraine symptom (nausea, light sensitivity, or sound sensitivity) resolved two hours after treatment; significantly greater among patients receiving Reyvow.


  • Risk of driving impairment
  • Most common side effects: Dizziness, fatigue, a burning or prickling sensation in the skin (paresthesia), sedation


  • Controlled Substance scheduling by DEA pending
  • Required pediatric assessments
  • Postmarketing requirement: Maternal, fetal, and infant outcomes during pregnancy exposure




SCENESSE (afamelanotide) implant


INDICATION: To increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP)

ADDRESSING UNMET NEED: First treatment to increase pain-free light exposure in patients with rare disorder phototoxic reactions from EPP

MECHANISM OF ACTION: Synthetic tridecapeptide and a structural analog of α-melanocyte stimulating hormone – melanocortin receptor agonist and binds predominantly to melanocortin 1 receptor.


  •  2 parallel group clinical trials (n-93, 74), patients with erythropoietic protoporphyria, SCENESSE vs placebo
  • First trial primary endpoint: Total number of hours over 180 days spent in direct sunlight between 10 a.m. and 6 p.m. on days with no pain; . 64 hrs vs. 41 hrs
  • Second trial primary endpoint: Total number of hours over 270 days spent outdoors between 10 am and 3 pm on days with no pain for which “most of the day” was spent in direct sunlight; 6 hrs vs. 0.75 hrs


  • Most common side effects: implant site reaction, nausea, oropharyngeal pain, cough, fatigue, skin hyperpigmentation, dizziness, melanocytic nevus , respiratory tract infection, somnolence, non-acute porphyria, skin irritation


  • Priority Review, Orphan Drug designation
  • Postmarketing requirements: Thorough QT clinical study, Registry based observational exposure cohort study on long-term safety,


Image credits: OraSure, Vertex, Eli Lilly, Clinuvel



News & Views: CDRH women health plan, ASCA, ALS guidance, Patient engagement, Limited Imodium packaging, Improving naloxone access, Premarket Tobacco Product Applications, Project Orbis


CDRH: Health of Women Strategic Plan

  • Explores unique issues related to the performance of medical devices in women
  • Improves analysis and communication of sex- and gender-specific data to better assure the safe and effective use of medical devices
  • Develops and implements health science programs, strategies and initiatives focused on women’s health issues across CDRH



The Accreditation Scheme for  Conformity Assessment (ASCA): Pilot Program

Under ASCA Pilot’s conformity assessment scheme, recognized accreditation bodies accredit testing laboratories for the competence of testing and calibration laboratories

  • ASCA-accredited testing laboratories may determine conformance of device with eligible standards
  • Provide declaration of conformity  to support  premarket submission


  • Development of the ASCA pilot
  • Conformity assessment resources leveraged in ASCA Pilot
  • Roles and Responsibilities: Accreditation bodies, Testing laboratories, Manufacturers, FDA staff
  • Selected Device Standards
  • Accreditation body and Testing Laboratory Participation



Amyotrophic Lateral Sclerosis Guidance

ALS is progressive neurodegenerative disease that primarily affects motor neurons in cerebral motor cortex, brainstem, spinal cord, leading to loss of voluntary movement

  • Guidance focuses on specific clinical drug development and trial design issues that are unique to the study of ALS


  • Early Phase Clinical Development, Population,  Effectiveness and Safety Considerations.
  • Specific Effectiveness Trial : Trial design, effectiveness endpoints,  timing of assessments, statistical considerations., prognostic factors,  integrated assessment of function and survival, Accelerated Approval considerations, Benefit-Risk considerations.



Patient Engagement in the Design and Conduct of Medical Device Clinical Investigations

FDA values experience and perspectives of patients and their family caregivers. Draft guidance scope:

  • Use patient engagement to elicit experience, perspectives from patient advisors to improve design and conduct of medical device clinical investigations
  • Benefits of engaging with patient advisors
  • Patient engagement activities not considered by FDA to constitute research
  • Collecting and submitting patient engagement information



Limited packaging for loperamide (Imodium) to encourage safe use

Reports of serious heart problems and deaths with much higher than the recommended doses of loperamide

  • Primarily among people intentionally misusing or abusing the product

To foster safe use of the over-the counter (OTC) anti-diarrhea drug loperamide

  • Use blister packs or other single dose packaging and to limit the number of doses in a package



Continued efforts to increase availability of all forms of naloxone to help reduce opioid overdose deaths

Addressing opioid overdose continues to be one of the most urgent public health priorities

  • Naloxone is a critical tool for individuals, families, first responders and communities to help reduce opioid overdose deaths
  • Three FDA-approved forms of naloxone – injectable, auto-injector and nasal spray – require a prescription, which can be a barrier

Steps to improve access to naloxone (Narcan)

  • Pharmacists given direct authority to prescribe and sell naloxone to consumers
  • Community distribution and use by individuals with or without medical training
  • Approveal of first generic version of Narcan
  • Encouraging development of OTC naloxone products.



Proposed rule for premarket tobacco product applications as part of commitment to continuing strong oversight of e-cigarettes and other tobacco products

Premarket tobacco product applications (PMTAs) for oversight of e-cigarettes and other tobacco products. Provide sufficient information on 

  • Physical aspects of a tobacco product
  • Potential public health benefits and harms
  • Also review tobacco product’s components, ingredients, additives, constituents, toxicological profile and health impact, as well as how the product is manufactured, packaged and labeled
  • Establish requirements for manufacturers to maintain records related to the legal marketing status of their tobacco products



FDA takes first action under new international collaboration with Australia and Canada designed to provide a framework for concurrent review of cancer therapies

Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE), provides  framework for concurrent submission and review of oncology products among international partners

  • May allow cancer patients receive earlier access to drkugs
  • Greater uniformity of new global standards of treatment leading to the optimal design of  global clinical trials

First Project Orbis action in conjunction with the Australian Therapeutic Goods Administration and Health Canada

  • Accelerated approval to Lenvima (lenvatinib) in combination with Keytruda (pembrolizumab) for treatment of advanced endometrial carcinoma
  • Also used ‘Real-Time Oncology Review’ (RTOR) pilot program, which can streamline the submission of data prior to the completion and submission of the entire clinical application


Image credits: FDA, CDC

News & Views: AEDs, Office on New Drugs reorganization, New digital health policies, Office of Women’s Health, THC vapes warning


Check Your AED: Is it FDA Approved?

Automated external defibrillators (AEDs) are portable, life-saving devices designed to treat sudden cardiac arrest,

  • Public access AEDs used by laypeople who have received minimal training
  • Professional use AEDs  used by first responders who receive additional AED training

Premarket approval (PMA) now required new and existing AEDs and necessary AED accessories batteries, pad electrodes, adapters and hardware keys for pediatric use)- deadline Feb 3, 2020

  • To ensure the quality and reliability
  • Needs sufficient valid scientific evidence to reasonably assure the device is safe and effective
  • Requires manufacturers to receive FDA approval before initiating design, manufacturing, or labeling changes to the device, imposes certain other annual reporting requirements.



Reorganization of the Office of New Drugs with Corresponding Changes to the Office of Translational Sciences and the Office of Pharmaceutical Quality

To modernize the New Drugs Regulatory Program – a reorganization of the New Drugs Regulatory Program

Restructuring of the Office of New Drugs (OND) and corresponding changes in the Office of Translational Sciences (OTS) and Office of Pharmaceutical Quality (OPQ)

  • Create offices that align interrelated disease areas, and divisions with clearer and more focused areas of expertise
  • Enable greater efficiency, better understand the diseases, enhance scientific leadership



New steps to advance digital health policies that encourage innovation and enable efficient and modern regulatory oversight

Guidances to continue to encourage innovative approaches to the development of digital health tools and advanced FDA oversight 

Clinical Decision Support Software, (revision)

  • Patients, families and health care professionals increasingly embracing digital health technologies to inform everyday decisions
  • Encourage developers to create, adapt and expand functionalities of software to support providers in diagnosing and treating diseases, while ensuring  no  unacceptable risk to patient
  • Focus our regulatory oversight on CDS functions intended to help health care professionals and patients inform their clinical management for serious or critical conditions- no independent evaluation of the basis of software’s recommendations

Changes to Existing Medical Software Policies Resulting from Section 3060 of the 21st Century Cures Act

  • Types of software that are no longer considered medical devices under the amended definition of device
  • Mobile apps that are intended only for maintaining or encouraging a healthy lifestyle – generally fall outside the scope FDA’s regulation



Critical Focus on Women’s Health

Office of Women’s Health established in 1994  to advance health of women through science, policy, education, outreach, and inclusion of women in clinical trials

  • Investing in Women’s Health Through Engagement and Education 
  • Fostering Scientific Research and Filling Knowledge Gaps
  • Advancing Medical Therapies that Meet Women’s Needs



FDA Warns Public to Stop Using Tetrahydrocannabinol (THC)-Containing Vaping Products and Any Vaping Products Obtained Off the Street

FDA strengthening warning to consumers to STOP using vaping products containing THC

  • More than 1,000 reports of lung injuries- including some resulting in deaths-following the use of vaping products
  • Most of the patients reported using THC-containing products, suggesting THC vaping products play a role in the outbreak

FDA Actions

  • Working closely with federal and state partners to identify the products or substances that may be causing the illnesses
  • FDA’s Forensic Chemistry Center using state-of-the-art technology to analyze hundreds of samples for the presence of a broad range of chemicals


Image credit: FDA

Drug Authorizations: JYNNEOS smallpox vaccine, RYBELSUS for Type 2 Diabetes, ERLEADA for Metastatic Prostate Cancer, OFEV for Interstitial Lung Disease


JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) suspension for subcutaneous injection

Bavarian Nordic A/S

INDICATION: Caccine indicated for prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection.

ADDRESSING UNMET NEED: Only currently FDA-approved vaccine for the prevention of monkeypox disease

  • Routine vaccination of the American public was stopped in 1972; thus a large proportion of the U.S., as well as the global population has no immunity
  • Reflects U.S. government’s commitment to preparedness for intentional release of this highly contagious virus

MECHANISM OF ACTION: Live vaccine produced from the strain Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), an attenuated, non-replicating orthopoxvirus; elicits humoral and cellular immune responses to orthopoxviruses


  • Clinical study, n=400 healthy adults, 18 -42 years, never been vaccinated for smallpox
  • Endpoint: Noninferior immune responses with Jynneos vs.  ACAM2000, an FDA-approved vaccine smallpox prevention
  • Supportive data from non-human primates – Jynneos protected from exposure to viruses related to the smallpox virus.
  • Monkeypox effectiveness:  Antibody responses in smallpox clinical study participants and in non-human primates


  • N>7,800 individuals receiving at least one dos
  • Commonly reported side effects: Pain, redness, swelling, itching, firmness at the injection site, muscle pain, headache and fatigue


  • Priority Review and material threat medical countermeasure (MCM) priority review voucher
  • Vaccine also part of the Strategic National Stockpile (SNS), the nation’s largest supply of potentially life-saving pharmaceuticals and medical supplies for use in a public health emergency



RYBELSUS (semaglutide) oral tablets 

Novo Nordisk

INDICATION: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

ADDRESSING UNMET NEED: First glucagon-like peptide (GLP-1) receptor protein treatment approved that does not need to be injected

MECHANISM OF ACTION: Acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1


  • Several clinical trials, placebo-controlled and compared to other GLP-1 injection treatments, stand-alone therapy and in combination with other diabetes treatments, paitents with Type 2 diabetes
  • In the placebo-controlled studies: Aignificant reduction in blood sugar (hemoglobin A1c);  after 26 weeks, 69%  – 77% on Rybelsus decreased their HbA1c to < 7%, vs.  31% on placebo


  • Boxed warning:  Increased risk of thyroid c-cell tumors including medullary thyroid carcinoma (MTC)
  • Warnings: Pancreatitis,  Diabetic retinopathy, hypoglycemia, acute kidney injury and hypersensitivity reactions
  • Most common side effects: Nausea, diarrhea, vomiting, decreased appetite, indigestion and constipation


  • Required  pediatric assessments: 52-week, randomized, double-blind, placebo-controlled parallel group study in pediatric patients ages 10-17
  • Postmarketing requirement: Medullary thyroid carcinoma registry-based case series of at least 15 years duration



ERLEADA (apalutamide) tablets


INDICATION FOR USE:  For treatment of Metastatic castration-sensitive prostate cancer (mCSPC)


  • Randomized, double-blind, placebo-controlled, multi-center clinical trial, n= 1,052 patients with mCSPC, Erleada vs . placebo
  • Major efficacy outcome: Overall Survival (OR) and radiographic progression-free survival (rPFS) . Statistically significant improvements in OS (hazrad ratio 0.67),  p=0.0053;  rPFS (hazard ratio 0.48), p<0.0001
  • Most common adverse reactions:  Fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture


  • Initially approved for non-metastatic prostate canacer
  • Used OCE’s Real-Time Oncology Review (RTOR) pilot program and accompanying Assessment Aid
  • Granted priority review



OFEV  (nintedanib) capsules

Boehringer Ingelheim

INDICATION: To slow the rate of decline in pulmonary function in patients with systemic sclerosisassociated interstitial lung disease (SSc-ILD).


  • ~ 100,000 US individuals have scleroderma, and ~ half of scleroderma patients have interstitial lung disease associated SSc-ILD
  • Slows rate of decline in pulmonary function in SSc-ILD

MECHANISM OF ACTION: IUnhibits multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs); blocks intracellular signaling which is crucial for proliferation, migration, transformation of fibroblasts related to IPF pathology


  • Randomized, double-blind, placebo-controlled trial, n=576 patients, 20-79 years with disease, treatment for 52 weeks – up to 100 weeks
  • Primary endpoint: .Forced vital capacity (FVC) – a measure of lung function, defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible
  • Less lung function decline with Ofev vs placebo



  • Most frequent serious adverse event: Pneumonia, diarrhea
  • Warnings: Moderate or severe hepatic impairment,  embryo-fetal toxicity


  • Originally approved in 2014 for idiopathic pulmonary fibrosis (IPF), which is another interstitial lung condition

    Received Priority Review designation, Orphan Drug designation


Image credits: Bavarian Nordic, Novo Nordisk, Janssen, Boehringer Ingelheim

Vaping Illnesses


Vaping Illnesses: Consumers can Help Protect Themselves by Avoiding Tetrahydrocannabinol (THC)-Containing Vaping Products

  • Consumers are likely aware of the recent reports of respiratory illnesses — including some resulting in deaths – following the use of vaping products
  • FDA remains deeply concerned about these incidents and is working closely with CDC, state and local public health partners to investigate
  • More information needed to better understand whether there’s relationship between specific products or substances and reported illnesses
  • CDC and the FDA encourage the public to submit detailed reports of any unexpected tobacco- or e-cigarette-related health or product issues to the FDA via the online Safety Reporting Portal.


image credit: FDA

Biosimilars Basics


New patient webpage o help increase awareness of and understanding of Biosimilars

  • Basic definitions: biological medications, biosimilar medications, and other terms to facilitate understanding the relationship between biosimilars and the original (reference) medications they are compared to
  • Increase awareness: FDA-approved biosimilar medications are safe and effective medications for treating many illnesses such as chronic skin and bowel diseases, arthritis, kidney conditions, and cancer
  • Provide details: How biosimilar medications can benefit patients


Image credit: FDA

2019 FDA Science Forum


2019 FDA Science Forum

2019 FDA Science Forum entitled Transforming Health: Innovation in FDA Science  with topic areas

  1. Precision Health: For individuals and special populations
  2. Advanced Technology: 3D printing and nanomaterials
  3. Product Accessibility, Integrity, and Security: Theory, modeling, methodology
  4. Predictive Tools: In vitro/in vivo assays and computational modeling
  5. Advancing Digital Health and Artificial Intelligence: Artificial intelligence and evaluating digital health devices
  6. Outbreak! Prevention through cybersecurity, promoting medical product security, rapid response to infectious disease outbreaks
  7. Addiction: Neurobiology, opioids, cannabinoids, nicotine
  8. Empowering Consumers, Patients, and Other Stakeholders: Science of patient input.


Image credit: FDA

News & Views: Patient-Focused drug development, Benefit-Risk for weight loss devices, Humanitarian Device Exemption, Warning for umbilical cord blood products, Special 510(k) program, Warning to JUUL, Safer Technologies Program


Patient-Focused Drug Development (PFDD) Guidance Series for Enhancing the Incorporation of the Patient’s Voice in Medical Product Development and Regulatory Decision Making

Series of four methodological guidance documents to collect and submit patient experience data and other relevant patients and caregivers information

  1. Collecting Comprehensive and Representative Input
  2. Methods to Identify What is Important to Patients
  3. Selecting, Developing or Modifying Fit-for-Purpose Clinical Outcome Assessments
  4. Incorporating Clinical Outcome Assessments into Endpoints for Regulatory Decision M​aking​


Capture.JPGConsideration of Benefit-Risk Approaches for Weight-Loss Devices

Proposal for assessing tolerability of risk in light of varying degrees of effectiveness for devices intended for weight loss


  • Weight loss: Amount of weight loss, proportion of patients experiencing weight loss, durability of weight loss
  • Changes in comorbidities: Clinically significant reduction in HbA1c18, hypertension, and/or hyperlipidemia


  • Adverse events: Severity, types, numbers, rates, duration 
  • Long-term effects of the device permanent implantation, anatomic changes, restriction of future treatment options, reversibility limitations
  • Clinical treatments/procedures related to the device: Expected concomitant medications or therapies, rate of early device removal, risks related to placement/removal procedures



Humanitarian Device Exemption (HDE) and Humanitarian Use Devices (HUDs)

Devices intended to benefit US patients in the treatment or diagnosis of diseases or conditions that affect or are manifested in not more than 8,000 individuals per year

  • Will not expose patients to an unreasonable or significant risk of illness or
    injury, and probable benefit to health outweighs the risk
  • Would not be available to a person with the disease or condition in question
    without the HDE; No comparable device

Scope of guidance:

  • FDA Review Actions
  • Assessing Probable Benefit and Risk
  • Post-Approval Requirements
  • Special Considerations for Devices Marketed Under an HDE
  • Appendices to support the HDE Program: Filing Checklist, Probable Benefit-Risk Assessment Summaries


Capture.JPGUnapproved Stem cell therapy – Warning to Stemell for selling unapproved umbilical cord blood and umbilical cord products that may put patients at risk

Warning to Stemell, Inc. (Stemell), CA, for products derived from umbilical cord blood and umbilical cord: StemL UCB-Plus and StemL UCT-Plus

  • Significant deviations from current good tissue practice (CGTP) and current good manufacturing practice (CGMP) requirements
  • Deficient donor eligibility practices and environmental monitoring
  • Creating potential significant safety concerns that put patients at risk

False claim that stem cell products don’t fall under the regulatory provisions for drugs and biological products



Special 510(k) Program

Facilitate submission, review, clearance of change to manufacturer’s own legally marketed predicate device (“existing device”) authorized through 510(K) or De Novo

  • Performance data are unnecessary
  • If performance data are necessary, well-established methods are available
  • All performance data necessary to support SE can be reviewed in a summary or risk analysis format




Warning to JUUL Labs for marketing unauthorized modified risk tobacco products, including in outreach to youth

For marketing unauthorized modified risk tobacco products

  • Engaging in labeling, advertising, and/or other activities directed to consumers
  • Presentation given to youth at a school.

Requesting more information, about several issues raised in a recent Congressional hearing regarding JUUL’s outreach and marketing practices

  • Targeted at students, tribes, health insurers and employers

Part of series of FDA actions for providing strong oversight of e-cigarettes and other electronic nicotine delivery systems (ENDS) 



Safer Technologies Program (STeP) for Medical Devices

To spur innovation towards safer medical devices and was modeled after the Breakthrough Devices Program

  • For PMA, De Novo and 510(K) pathways; Devices and device-led combination products
  • Should be reasonably expected to significantly improve the benefit-risk profile
  • reduction in the occurrence of a known serious adverse event
  • reduction in the occurrence of a known device failure mode
  • reduction in the occurrence of a known use-related hazard or use error
  • improvement in the safety of another device or intervention.


  • Interactive and timely communications with the FDA, review team support, senior management engagement
  • Prioritized review
  • May reduce the total time to develop a device and achieve marketing authorization, while still meeting the agency’s gold standard for safety and effectiveness


Image credit: FDA

News & Views: New health warnings on cigarette packages, Investigation of respiratory illnesses with e-cigarette use, Duodenoscopes with enhanced safety, Uncertainty in device benefit-risk determinations, Benefit-Risk determinations in De Novo classifications, Drugs for male breast cancer, Expediting access to drugs


New required health warnings with color images for cigarette packages and advertisements to promote greater public understanding of negative health consequences of smoking

Science-based approach to develop and evaluate the new proposed cigarette health warnings

  • Focus on serious health risks – such as bladder cancer, diabetes, erectile dysfunction and conditions that can cause blindness


CaptureFederal and CDC collaboration to investigate respiratory illnesses reported after use of e-cigarette products

FDA and CDC collaborating to investigate incidents of severe respiratory disease associated with use of e-cigarette products

  • Updating the number of potential cases of respiratory illnesses after use of e-cigarette products
  • Sharing more details about CDC and FDA work
  • Providing public and health partners across the country with information to help mitigate risk of additional incidents

More information needed to better understand relationship between specific products and reported illnesses

  • THC and cannabinoids use reported in many cases
  • e-cigarette products should not be used by youth, young adults, pregnant women, and adults who do not currently use tobacco products


Capture.JPGTransition to Duodenoscopes with Innovative Designs to Enhance Safety

  • Duodenoscopes used in more than 500,000 endoscopic retrograde cholangiopancreatography (ERCP) procedures each year
  • Have complex designs with reusable hard-to-clean components
  • Failure to correctly reprocess duodenoscope could result in patient-to-patient disease transmission
  • Recommendation to use duodenoscopes with innovative device designs that make reprocessing easier, more effective, or unnecessary. (e.g. Fujifilm Corporation, Duodenoscope model ED-580XT, Pentax Medical, Duodenoscope model ED34-i10T)



Consideration of Uncertainty in Making Benefit-Risk Determinations in Medical Device Premarket Approvals, De Novo Classifications, and Humanitarian Device Exemptions

In premarket decision-making for devices, there exists some uncertainty around benefits and risks – type, magnitude, duration, frequency, other aspects

Appropriate uncertainty in a benefit-risk determination would depend on totality of information covering several factors

  • Extent of probable benefits of the device – magnitude, probability, duration, frequency
  • Extent of probable risks of the device- severity, type, number, rates, probability,  duration
  • Extent of uncertainty of benefit-risk profile of  precedent devices
  • Patients’ perspective on appropriate uncertainty
  • Extent of the public health need
  • Feasibility of generating extensive premarket clinical evidence
  • Ability to reduce or resolve remaining uncertainty postmarket
  • Effectiveness of mitigations, such as labeling, and other tools
  • Type of decision being made (e.g., HDE vs PMA)
  • Probable benefits of earlier patient access to the device



Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications




Male Breast Cancer: Developing Drugs for Treatment

Breast cancer is rare in males (<0.1%),  diagnosed at an older age, with more advanced stage of disease, and more likely to have lymph node involvement 

  • Eligibility criteria for clinical trials of breast cancer drugs should allow for inclusion of both males and females
  • May be possible to extrapolate findings to male patients where no difference in efficacy or safety between males and females is anticipated



Delivering Promising New Medicines Without Sacrificing Safety and Efficacy

Congress has established five programs to expedite patient access to drugs that treat serious or life-threatening conditions while maintaining FDA’s gold standard of safety and efficacy

To assist drug development

  • Fast Track designation:  Drug is intended to treat a serious disease and that laboratory, animal model, or human data show promise
  • Breakthrough Therapy designation:  Preliminary clinical evidence indicates that  drug may demonstrate substantial improvement over available therapy
  • Regenerative Medicine Advanced Therapy designation (RMAT): Preliminary clinical evidence indicates regenerative medicine therapy has potential to address unmet medical needs for such condition

To expedite FDA review timelines: 

  • Priority Review designation FDA aims to take action on a marketing application within six months, compared to 10 months under standard review. Only granted if  data submitted in the marketing application appear to show a significant improvement in safety or effectiveness for a serious condition

Different route for expediting:

  • Accelerated Approval: Approval of a drug that demonstrates an effect on a “surrogate endpoint” that is reasonably likely to predict clinical benefit


Image credit: FDA

AUTHORIZATIONS: ROZLYTREK for cancers with specific genetic defect, PRETOMANID for multidrug resistant TB, TURALIO for tenosynovial giant cell tumor, NUBEQA for castration resistant prostate cancer


ROZYLTREK (entrectinib)

Genentech, Inc.


  • ROS1-Positive Non-Small Cell Lung Cancer : Treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive.
  • NTRK Gene Fusion-Positive Solid Tumors: Treatment of adult and pediatric patients 12 years of age and older with solid tumors that:
    • have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation
    • are metastatic or where surgical resection is likely to result in severe morbidity, and
    • have either progressed following treatment or have no satisfactory alternative therapy.

Approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.


  • “Tissue agnostic” cancer treatment based on a common biomarker across different types of tumors rather than  body location
  • Innovation in precision oncology drug development, targeted and effective treatments
  • Simultaneous approvals in adult and pediatric populations

MECHANISM OF ACTION: Inhibitor of the tropomyosin receptor tyrosine kinases (TRK), proto-oncogene tyrosine-protein kinase ROS1, naplastic lymphoma kinase (ALK), JAK2 and TNK2. Inhibits tumorigenic potential through deactivation of downstream signaling pathways leading to constrained cell proliferation


  • Four clinical trials studying, n= 54 with NTRK fusion-positive tumors
  • Overall Response Rate (tumor shrinkage) of 57%; 7.4% having complete disappearance of the tumor; 61% with tumor shrinkage persisting for nine months or longer.
  • Most common cancer locations: Lung, salivary gland, breast, thyroid, colon/rectum

For non-small cell lung cancer,  with ROS1-positive and metastatic

  • Clinical studies, n= 51 with ROS1-positive lung cancer
  • Overall response rate: 78%, 5.9% with complete disappearance of cancer, 55% had tumor shrinkage persist for 12 months or longer


  • Most serious side effects: Congestive heart failure, central nervous system effects, skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation, vision disorders
  • Common side effects: Fatigue, constipation, dysgeusia, edema , dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, weight gain, cough, vomiting, fever, arthralgia, vision disorders


  • Accelerated approval. .Priority ReviewBreakthrough Therapy and Orphan Drug designation
  • Postmarketing requirements: Clinical studies that further characterize clinical benefit, functional activation or inhibition of off-target receptors, transporters, and/or channels, integrated safety analyses and supporting data, effect of moderate and severe hepatic impairment



The Global Alliance for TB Drug Development (TB Alliance)

INDICATION: Limited Population: Part of a combination regimen with bedaquiline and linezolid for the treatment of adults with pulmonary extensively drug resistant (XDR) or treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB).  Approval of this indication is based on limited clinical safety and efficacy data.

Indicated for use in limited and specific population of patients


  • Multidrug-resistant TB and extensively drug-resistant TB are public health threats due to limited treatment options
  • estimated 490,000 new cases of multidrug-resistant TB worldwide, with a smaller portion of cases of extensively drug-resistant TB
  • New treatments are important to meet patient national and global health needs

MECHANISM OF ACTION: Nitroimidazooxazine antimycobacterial drug


  • Open-label study conducted in three centers in South Africa, n=109 with extensively drug-resistant, treatment intolerant or non-responsive multidrug-resistant pulmonary TB (of the lungs), taken orally in combination with bedaquiline and linezolid, 6 months
  • Endpoint: Incidence of bacteriologic failure (reinfection – culture conversion to positive status with different M. tuberculosis strain), bacteriological relapse (culture conversion to positive status with same M. tuberculosis strain), or clinical failure through follow-up until 6 months after the end of treatment
  • Successes (lack of failure) : 89%, significantly exceeded the historical success rates or treatment of extensively drug resistant TB


  • Most common adverse reactions:  Peripheral neuropathy, acne, anemia, nausea, vomiting, headache, increased liver enzymes, dyspepsia, rash, increased pancreatic enzymes, hypoglycemia, diarrhea


  • Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD)pathway
  • Qualified Infectious Disease Product (QIDP) designation, Priority Review, Orphan Drug designation
  • Awarded Tropical Disease Priority Review Voucher 


CaptureTURALIO (pexidartinib) capsules

Daiichi Sankyo

INDICATION: Treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery

ADDRESSING UNMET NEED: TGCT is a rare tumor that affects the synovium and tendon sheaths causing damage to surrounding tissue

MECHANISM OF ACTION: Tyrosine kinase inhibitor that targets colony stimulating factor 1 receptor (CSF1R); inhibition of proliferation of cell lines dependent on CSF1R and ligand-induced autophosphorylation of CSF1R


  • Multi-center international clinical trial, n=120 patients, TURALIO vs. placebo
  • Primary efficacy endpoint: Overall response rate (ORR) analyzed after 25 weeks
  • Statistically significant improvement in ORR: 38% on TURALIO vs 0% on placebo
  • Complete response rate: 15%, Partial response rate: 23%


  • Boxed Warning: Risk of serious and potentially fatal liver injury. REMS program
  • Common side effects: Increased lactate dehydrogenase, increased aspartate aminotransferas, loss of hair color, increased alanine aminotransferase, increased cholesterol


  •  Breakthrough Therapy designation,  Priority Review designation, Orphan Drug designation
  • Postapproval commitments: Further evaluate the risk of hepatoxicity
  • REMS to prevent potentially fatal liver toxicity: To include (i) Communication Plan and (ii)  Elements to  Assure Safe Use


Capture.JPGNUBEQA (darolutamide) tablets


INDICATION: Treatment of patients with non-metastatic castration resistant prostate  cancer (nmCRPC)

MECHANISM OF ACTION: Androgen receptor (AR) inhibitor


  • Multicenter, double-blind, placebo-controlled clinical trial, n=1,509 patients with non-metastatic castration resistant prostate cancer, NUBEQA vs. placebo, all  received gonadotropin-releasing hormone (GnRH) analog concurrently or had previous bilateral orchiectomy
  • Primary endpoint: Metastasis free survival (MFS)
  • 40.4 months with darolutamide vs. 18.4 months with placebo,  p<0.0001


  • Most common adverse reactions: Fatigue, pain in extremity, and rash
  • Other: Ischemic heart disease, failure, seizures


  • Fast track designation, Priority Review


Image credits: Genentech, TB Alliance, Daiichi Sankyo, Bayer








News & Views: Novartis Data Accuracy Issues, e-cigarettes and seizures, Topical drugs bioequivalence, Drug safe importation


Data accuracy issues with Zolgensma, manufactured by AveXis (Novartis)

  • On May 24, the FDA approved Zolgensma, a gene therapy product intended to treat children less than two years of age with spinal muscular atrophy (SMA)
  • On June 28, the agency was informed by AveXis Inc (Novartis subsidiary), about  data manipulation issue of data submitted in the BLA for the approval
  • Thus FDA approved Zolgensma without knowledge of data manipulation; the Agency continues to be supportive of the benefit-risk profile at this time
  • However, the Agency is concerned about the delay in notification by Novartis
  • Ensuring truthful, complete and accurate data in product applications is a critical component of industry responsibility
  • There will be further inspections and investigations and will take action including civil or criminal penalties

FDA 483 Inspection Report


Capture.JPGSeizures following e-cigarette use as part of agency’s ongoing scientific investigation of potential safety issue

  • Continuing FDA scientific investigation on direct relationship between e-cigarettes and risk of seizure or other neurological symptoms
  • 127 reports on e-cigarette users experiencing seizures (between 2010-2019)
  • Some users reported other serious neurological symptoms e.g. fainting, tremors
  • FDA requesting use of Safety Reporting Portal   for any unexpected health or product issues experienced with e-cigarettes


Capture.JPGEvaluating bioequivalence for topical drugs

  • FDA research initiative to facilitate generic topical dermatological drug product development
  • New method for monitoring amount of topical drug in dermis using dermal open-flow microperfusion (dOFM)
  • Thin, hollow porous tube inserted just under the skin surface, liquid similar to body fluid is injected, any applied drug absorbed through the skin’s outer layer enters  flowing liquid, which is then collected for analysis
  • Clinical study performed to confirm dOFM could reliably measure changing amounts of drug in skin after topical application of dermatological drug products



 New Action Plan to Lay Foundation for Safe Importation of Certain Prescription Drugs

Two potential pathways for safe importation of certain drugs originally intended for foreign markets
  1. Pathway 1: Authorize importation of drugs from Canada with conditions to ensure  no additional risk to public’s health and safety
  2. Pathway 2: Import versions of FDA-approved drug products being sold in foreign countries that are the same as the U.S. versions; use a new National Drug Code
Safe Importation Action Plan – PDF*

Image credits: Novartis, FDA

News & Views: Software Precert program, Drug shortages and sterilization,CSF shunts & hearing aids, PrEP HIV program, Drug abuse labeling, EU inspection partnership, Weight management devices, Breast implant recall, Regulating E-Cigs


Software Precertification (Pre-Cert) Program Update

Pre-Cert program introduced to streamline regulation of  digital health devices, specifically software as a medical device (SaMD)

Test phase: Excellence Appraisal and Streamlined Review components

  • Mock Excellence Appraisal summary
  • Streamlined Review packages by extracting elements from original submission
  • Mock review on whether regulatory decision could be made


  • Regulatory decision could be made
  • Opportunities to simplify Excellence Appraisal and Streamlined Review process


Capture.JPGPreventing Medical Device Shortages by Ensuring Safe and Effective Sterilization in Manufacturing

Sterilization issues during manufacturing is cause of device shortages; steps to prevent

  • Monitoring  device supply, planning for and preventing potential shortages
  • Engaging with Healthcare Infection Control Practices Advisory Committee (HICPAC)
  • New innovation challenges for ideas from stakeholders, academics, industry
    • new or alternative sterilization methods
    • alternatives to those that use ethylene oxide


Programmable CSF Shunts and Magnetic Field Interference with Implanted Hearing Devices 

Magnetic interactions in patients implanted with both programmable  cerebrospinal fluid (CSF) shunt systems and hearing aids (cochlear implants, bone conduction hearing devices, or middle ear hearing devices)

  • May inadvertently change programmable CSF shunt valve settings
  • Altered mental status, headaches, lethargy, irritability, vomiting, changes in vision, and difficulty walking – could progress to seizures, hemorrhage, or even death


  • Educate patients and caregivers about potential risk
  • Check CSF shunt valve setting after placement or adjustment of other devices
  • Consider different placement of CSF shunt valve if patient has other implanted devices
  • Contact the applicable device manufacturer for further information


Capture.JPGPrEP and additional steps to help reduce the risk of getting HIV

Pre-exposure prophylaxis (or PrEP)  is for people at very high risk of HIV infection

  • Daily doses of Truvada (tenofovir and emtricitabine) that are used in combination with other medicines to treat HIV
  • FDA is  eliminating risk evaluation and mitigation strategy (REMS) for Truvada to improve accessibility  and patient uptake


Capture.JPGEnsuring Patient Safety and Drug Manufacturing Quality Through Partnership with European Union Regulators

Mutual Recognition Agreement (MRA) with EU to more effectively deploy inspectional resources across the globe

  • FDA has completed capability assessments of 28 EU member states
  • Created important efficiencies for risk-based site selection model for inspection
  • Considering to extend beyond human drug products to veterinary products, human vaccines, and plasma-derived drugs



Drug Abuse and Dependence Section of Labeling for Human Prescription Drug and Biological Products 

The primary role of DRUG ABUSE AND DEPENDENCE section of labeling is to convey information about potential for abuse, misuse, addiction, physical dependence, and tolerance

Controlled Substance : Under the Controlled Substances Act, For Which Controlled Substance Scheduling Is Pending, Not Controlled Under the Controlled Substances Act 

Abuse: Information on Abuse, Misuse, Addiction

Dependence: Information on Physical Dependence and Withdrawal, Tolerance



FDA resources on Weight-Loss and Weight-Management Devices

Therapies for weight-loss or weight-management range from healthy eating and exercise, to prescription medicine, medical devices and surgery.

FDA Webpage provides information about:

Capture.JPGAction to protect women from breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)

  • Requested Allergan, manufacturer of BIOCELL textured breast implant, to recall device due to the risk of BIA-ALCL
  • Allergan is moving forward with worldwide recall
  • safety communication for patients with breast implants, considering breast implants and their health care professionals

CaptureSteps to control E-Cigs

  • Restricting youth access to electronic nicotine delivery systems (ENDS, which includes products known as “e-cigarettes”)
  • Conducting retailer and manufacturer checks on restricting sales to youth
  • Increasing Requirements for ENDS Manufacturers for safety
  • Utilizing Premarket Review Requirements for market authorizations

Real Cost campaign


Image credits: FDA, Allergan

Market Authorizations: IB-STIM for Irritable Bowel Syndrome, PIQRAY for advanced or metastatic breast cancer, ZOLGENSMA for spinal muscular atrophy


Innovative Health Solutions

INDICATION FOR USE: Percutaneous electrical nerve field stimulator (PENFS) system intended to be used in patients 11-18 years of age with functional abdominal pain associated with irritable bowel syndrome (IBS). The IB-Stim is intended to be used for 120 hours per week up to 3 consecutive weeks, through application to branches of Cranial Nerves V, VII, IX and X, and the occipital nerves identified by transillumination, as an aid in the reduction of pain when combined with other therapies for IBS.


  • First medical device for reduction of functional abdominal pain in patients 11-18 years of age with irritable bowel syndrome (IBS) when combined with other therapies for IBS
  • Advancing the development of pediatric medical devices


  • Prescription-only device
  • Small single-use electrical nerve stimulator placed behind patient’s ear
  • Battery-powered chip that emits low-frequency electrical pulses to stimulate branches of certain cranial nerves continuously for five days
  • Stimulating nerve bundles in and around the ear is thought to provide pain relief
  • Patients can use the device for up to three consecutive weeks to reduce functional abdominal pain associated with IBS


  • Clinical study, n= 50 patients 11-18 years of age with IBS; IB-Stim vs placebo
  • Endpoint: Change from baseline to the end of the third week in worst abdominal pain, usual pain and Pain Frequency Severity Duration (PFSD) scores
  • Worst pain at baseline: Similar between the treatment and placebo groups
  • Greater change (improvement) in worst pain from baseline to week three in  IB-Stim group; effect also seen at weeks one and two
  • Greater change also demonstrated in composite PFSD scores from baseline to week three in the IB-Stim group compared to the placebo group.
  • 30% decrease in usual pain at the end of three weeks in 52% IB-Stim patients vs 30% placebo
  • Six patients reported mild ear discomfort and three patients reported adhesive allergy at the site of application
  • Contraindicated for patients with hemophilia, patients with cardiac pacemakers or those diagnosed with psoriasis vulgaris


Capture.JPGPIQRAY (alpelisib) tablets


INDICATION: In combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CAmutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen.

  • Also approved the companion diagnostic test: Therascreen PIK3CA RGQ PCR Kit to detect the PIK3CA mutation in a tissue and/or a liquid biopsy
  • Patients who are negative by the therascreen test using the liquid biopsy should undergo tumor biopsy for PIK3CA mutation testing.

ADDRESSING UNMET NEED: First PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer.

MECHANISM OF ACTION: Inhibitor of phosphatidylinositol-3-kinase (PI3K) with  activity predominantly against PI3Kα; inhibited the phosphorylation of PI3K downstream targets, induce an increase in estrogen receptor (ER) transcription in breast cancer cells


  • Randomized trial, n=572 postmenopausal women and men with HR-positive, HER2-negative, advanced or metastatic breast cancer
  • Addition of Piqray to fulvestrant significantly prolonged progression- free survival (median of 11 months vs. 5.7 months) in patients whose tumors had a PIK3CA mutation.



  • Common side effects: High blood sugar levels, increase in creatinine, diarrhea, rash, decrease in lymphocyte count in the blood, elevated liver enzymes, nausea, fatigue, low red blood cell count, increase in lipase (enzymes released by the pancreas), decreased appetite, stomatitis, vomiting, weight loss, low calcium levels, aPTT prolonged (blood clotting taking longer to occur than it should), hair loss
  • Monitor patients for severe hypersensitivity reactions (intolerance)


  • First novel drug approved under the Real-Time Oncology Review pilot program
  • Use of updated Assessment Aid, a multidisciplinary FDA review template for review consistency and reduced review time
  • Priority Review designation
  • Postmarketing Commitments: Overall survival data, drug interaction studies


Capture.JPGZOLGENSMA (onasemnogene abeparvovec-xioi) intravenous infusion


INDICATION: Adeno-associated virus vector-based gene therapy indicated for the  treatment of pediatric patients less than 2 years of age with spinal muscular atrophy *SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene

Limitations for use:

  • Safety and effectiveness of repeat administration not been evaluated
  • Use in patients with advanced SMA not been evaluated

ADDRESSING UNMET NEED:  First gene therapy approved to treat children less than two years of age with spinal muscular atrophy (SMA), a leading genetic cause of infant mortality

MECHANISM OF ACTION: Recombinant AAV9-based gene therapy designed to deliver copy of gene encoding the human SMN protein. SMA is caused by a bi-allelic mutation in the SMN1 gene, which results in insufficient SMN protein expression. Intravenous administration of ZOLGENSMA results in cell transduction and expression of SMN protein has beennobserved in two human case studies


  • Ongoing clinical trial and a completed clinical trial, n=36, patients with infantile-onset SMA, 2 weeks -8 months old
  • 19/ 21 patients remaining, age:9.4 -18.5 months; 13/19 at least 14 months of age
  • Compared to natural history of patients with infantile-onset SMA, patients treated with Zolgensma demonstrated significant improvement in ability to reach developmental motor milestones (e.g., head control and the ability to sit without support)


  • Boxed Warning: Acute liver injury
  • Most common side effects: Elevated liver enzymes and vomiting


  • Fast Track, Breakthrough Therapy, and Priority Review designations
  • Orphan Drug designation and rare pediatric disease priority review voucher,


Image credit:  Innovative Health Solutions, Novartis, AveXis

News & Views: Medical device reporting, Cannabidiol policy, Benefit-Risk framework for opioid analgesics, CDER modernization, New drug approval transparency, Heart Failure treatment, Complex Innovative Trial Design Program, Safety with paclitaxel-coated stents, Prostate tissue ablation devices

Capture.JPGCDRH efforts to increase transparency in medical device reporting 

CDRH is updating Medical Device Reporting (MDR) Program

  • End Alternative Summary Reporting (ASR) Program: Granted . exemption from individual medical device reports for well-known and well-established risks
  • Implement Voluntary Malfunction Summary Reporting (VMSR) Program   to efficiently detect potential safety signals
  • Modernize Manufacturer and User Facility Device (MAUDE) database
  • Actively engage in the National Evaluation System for health Technology (NEST)


Capture.JPG Sound, Science-based Policy on Cannabidiol

Apply  rigorous, science-based approach to products containing cannabis or cannabis-derived compounds, including cannabidiol (CBD)

  • Many unanswered questions about the science, safety, and quality of many of these products
  • If product being marketed to have a therapeutic effect – regulated as a drug subject to FDA review and authorization
  • If marketed as food, including dietary supplements- overarching goal of protecting consumers and  currently illegal

FDA Public Meeting on May 31st for stakeholders to share feedback and experiences. Remaining open questions:

  • Daily safe dose of CBD and variability depending on form
  • Drug interactions
  • Impacts to special populations – children, elderly, pregnant, lactating women
  • Long-term exposure risks


Capture.JPGBenefit-Risk framework for evaluating opioid analgesics

New draft guidance, “Opioid Analgesic Drugs: Considerations for Benefit-Risk Assessment Framework,”

  • Benefit-risk assessment framework to address opioid crisis with focus on  formal assessment of associated public health risks
  • Assess benefits and risks of proposed new opioid analgesics relative to already approved opioid and non-opioid analgesics
  • Provide information on mitigation of risks of overdose, abuse or addiction
  • Provide public health implications of product in terms of risks to non-patients, including members of the patient’s household, visiting relatives, friends, others
  • New REMS is safety profile different from already approved products


Capture.JPGModernizing FDA’s New Drugs Regulatory Program

Initiative to modernize the New Drugs Regulatory Program to better serve patients and  staff in their work to carry out center’s mission

  • Scientific Leadership: Grow scientific expertise;  clarify regulatory pathways 
  • Integrated Assessment: Whether applications meet legal & regulatory requirements
  • Benefit-Risk Monitoring: Monitor pre- and post- approval 
  • Managing Talent: Attract, develop, and retain outstanding people
  • Operational Excellence: Standardize workflow, business processes, roles, responsibilities
  • Knowledge Management: Facilitate identification, capture, distribution, effective use of information


Capture.JPGNew drug approval transparency efforts

Efforts to enhance transparency around our drug approval decisions

  • Focus on information to improve patient care and better inform health care professionals about the product
  • Posting portions of clinical study reports after a drug receives FDA approval
  • Requesting public comment about programs


Capture.JPGTreatment for hear failure: Endpoints for drug development

Guidance pertains primarily to treating both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF)

  • Mortality data: Primary efficacy and safety
  • Endpoints related to how patients feel and function: Evidence of effectiveness
  • Hospitalization and outpatient intervention: All-cause vs. cause-specific
  • Biomarkers and surrogate endpoints: For clinical benefit
  • Acute heart failure: Symptom relief
  • Heart failure with preserved ejection fraction
  • Pediatric population



Circulatory System Devices Panel recommendations on late mortality safety signal associated with paclitaxel-coated products

Panel met to discuss safety vs benefit of paclitaxel-coated balloons and paclitaxel-eluting stents used to treat peripheral arterial disease in the femoropopliteal arteries

  • Unanimously agreed that the aggregate data showed a mortality signal
  • Could not conclude that the late mortality signal represented a class effect
  • Missing data (vital status, repeat interventional treatments, paclitaxel exposure)  hindered interpretation of analyses
  • Could not identify patient subgroups that might be at particularly high (or low) mortality risk
  • Observed rates of both cardiovascular and non-cardiovascular death were higher in patients treated with paclitaxel-coated devices vs. uncoated devices
  • Precluded determination of relationship between paclitaxel dose and mortality
  • Preclinical animal data do not indicate a potential biological mechanism for the late mortality signal
  • Short-term benefits of paclitaxel-coated devices continue to outweigh the risks, and  devices should not be removed from market; Additional comments on post-market surveillance and labeling


Capture.JPGComplex Innovative Trial Design (CID) Program

The CID Pilot Program is designed to:

  • Facilitate the use of CID approaches in late-stage drug development
  • Use of complex adaptive, Bayesian, and other novel clinical trial designs
  • Promote innovation by allowing FDA to publicly discuss the trial designs considered through the pilot program, including trial designs for medical products that have not yet been approved by FDA.


Capture.JPGClinical investigations for prostate tissue ablation devices

Draft guidance to provide recommendations for high intensity ultrasound systems for prostate tissue ablation:

  • Complying with clinical testing special control under 21 CFR 876.4340(b)(8) for 510(k)s)
  • Collecting clinical data to support marketing submissions for new types of prostatic tissue ablation devices

Marketing authorization for a general indication for ablation of prostatic tissue

  • High intensity therapeutic ultrasound energy into prostate to thermally ablate  defined, targeted volume of tissue
  • Achieve same clinical effect of ablating targeted tissue volumes using different sources of energy
  • Does NOT address intended uses for the treatment of a specific disease (e.g., prostate cancer or benign prostatic hyperplasia)


Image credit: FDA

FDA’s New History Exhibit


Forward Into the Past With FDA’s New History Exhibit

First permanent exhibit documenting the FDA’s history at the White Oak headquarters in Silver Spring, MD.

  • Includes many of the noteworthy achievements in the FDA’s long history
  • FDA continues to understand and learn from its history, to inform its work
  • Experience the new exhibit to gain better understanding of how FDA has evolved over the years and how its history continues to pave the way for the future



Image credit: FDA on Flickr




Webpage: Patient-Reported Outcomes (PROs) in Medical Device Decision Making


Patient-Reported Outcomes (PROs) in Medical Device Decision Making

This web page focuses on the use of patient-reported outcomes (PRO) as one type of patient input.

  • What Are Patient-Reported Outcomes
  • How CDRH Uses PROs in Regulatory Decision Making
  • CDRH Collaborations, Studies, Articles, and Workshops on Patient-Reported Outcomes
  • How to Incorporate Patient-Reported Outcome Measures (PROMs) in a Regulatory Submission


Image credit: FDA

News & Views: Measles vaccine, Interchangeable biosimilars, Warning for vaping social influencers, Project Facilitate for expanded access, Enhancing diversity of clinical trials, Fixed-quantity packaging for opioids, Safety throughout drug’s lifecycle, Participation in Pre-Cert program, Better prescription drug advertising, Global drug quality

CaptureVaccination Is the Best Protection Against Measles

Measles, Mumps, and Rubella Virus Vaccine Live (M-M-R II, commonly called MMR)

  • For people ages 12 months and older
  • Two doses of the vaccine is about 97% effective at preventing measles

Measles, Mumps, Rubella and Varicella Virus Vaccine Live (ProQuad, commonly called MMRV)

  • For children ages 1 through 12 years.
  • Also prevents chickenpox


CapturePolicy advancements to help bring interchangeable biosimilars to market

Pathway for “interchangeable” biologics

  • Substituted without the involvement of the prescriber
  • Similar to how generic drugs are routinely substituted for brand name drugs

 Final guidance on the pathway for “interchangeable” biologics

  • Overview of important scientific considerations in demonstrating interchangeability
  • Biological product is biosimilar to reference product and produces same clinical result
  • Risk of safety or diminished efficacy of alternating or switching will not be greater than the risk of using the reference product without such alternation or switch


Capture.JPGActions for violations by online posts on flavored e-liquids by social media influencers

FDA and FTC  warning letters to four firms that manufacture, sell, advertise flavored e-liquid products for social media influencers

  • Violations related to online posts by social media influencers on each company’s behalf, including failure to include the required nicotine warning statement
  • Enforcement action to address increased popularity of e-cigarettes among youth leading to health concerns, nicotine addiction, and more likely to transition to conventional cigarettes


Capture.JPGProject Facilitate to assist physicians seeking access to unapproved therapies for patients with cancer

New pilot program to assist oncology health care professionals in requesting access to unapproved therapies for patients with cancer

  • New call center called Project Facilitate as a single point of contact
  • Help submit Expanded Access request for an individual patient, including follow-up of patient outcomes
  • Expanded Access is pathway for treatment by investigational treatment outside of clinical trials for immediately life-threatening or serious disease or condition
  • Expanded Access requests help weigh whether potential benefit of investigational treatment justifies the potential risks



Draft Guidance for Industry on Enhancing the Diversity of Clinical Trial Populations

  • More inclusive trial practices, trial designs, and methodological approaches to broaden eligibility criteria
  • Increase enrollment of more diverse populations in clinical trials
  • Maximizes generalizability of trial results
  • Better understand therapy’s benefit-risk profile across the patient population likely to use the drug in clinical practice, without jeopardizing patient safety
  • Reflects FDA policy encouraging inclusion in clinical trials of participants representative of the broad population of patients including minorities


CaptureFixed-quantity blister packaging for certain opioid pain medicines to help decrease unnecessary exposure to opioids

Misuse of prescription opioids by getting them from a friend or family member


  • >191 million opioid prescriptions dispensed to ~ 60 million patients, either as first-time prescriptions or refills; ~ 90% patients reported not finishing what was prescribed to them

Special opioid packaging for reducing unused doses available for misuse, abuse, inappropriate access, accidental poisoning or overdose- considertions

  • Actual opioid use compared to prescribed amounts for common surgical procedures and acute pain conditions

  • 5-, 10-, and 15-Count Blister Packages of Certain IR Opioid and IR Opioid/Acetaminophen Products

  • New Packaging/Disposal REMS Element

  • Safety-Enhancing Benefits of Fixed-Quantity Blister Packaging for Opioid Analgesics for Treatment of Acute Pain

  • National Academies of Sciences, Engineering, and Medicine (NASEM) to help advance guideline development

Remove the Risk” campaign


Capture.JPGTracking and Acting on Safety Data Throughout a Drug’s Lifecycle

Agency tracks, analyzes and acts on the adverse event data collected over time to discover and communicate new risks associated with approved drugs 

  • Reports from patients, health care professionals and manufacturers about adverse events in  FDA Adverse Event Reporting System (FAERS)
  • Monitor FAERS database to identify safety signals, analyze and interpret data, combine with other scientific information for decision-making
  • If new risk confirmed, require addition to product’s label and may require a Risk Evaluation Mitigation Strategy (REMS) to ensure benefits outweigh risks
  • From 2002 through 2014, new safety issues discovered and added to labels for 278 drugs


CaptureParticipation in 2019 Test Plan for Digital Health Software Precertification (Pre-Cert) Program

Agency seeking test cases from software organizations planning to submit a De Novo Request or 510(k) submission for software as a medical device (SaMD)  to meet the goals of the Test Plan

  • Small and large software development firms
  • Companies that develop a range of products, including both low- and high-risk SaMD
  • Companies that are not considered to be traditional medical device manufacturers but who intend to make SaMD


Capture.JPGHelping to Better Communicate the Risks and Benefits in Prescription Drug Advertising

Direct-to-consumer advertising influence awareness of prescription drug treatments, influence patients and doctors

  • Using eye-tracking technology, researchers are examining elements of these ads that can affect the viewer’s ability to understand risks and benefits
  • With high-distraction ad – less able to recall or recognize risks described, spent less time on written statement of risks
  • Objective to help drug companies develop ads that better inform public


CaptureAssuring Drug Quality Around the Globe

Programs to address the challenges to drug quality posed by globalization to protect patients and consumers

  • Tools to assure continued safety, effectiveness, quality post-approval
  • Same quality for both domestic and foreign manufactured products
  • Addressing quality inspections and issues


Image credit: F DA 


Device Authorizations: MONARCH system for ADHD, XVIVO system for lung transplantation, COMANECI for intracranial aneurysms, NERIVIO MIGRA for migraine, ZIKV Detect 2.0 for Zika virus detection


MONARCH external Trigeminal Nerve Stimulation (eTNS) System


INDICATION FOR USE: Treatment of pediatric Attention Deficit Hyperactivity Disorder (ADHD) as a monotherapy in patients ages 7 through 12 years old who are not currently taking prescription ADHD medications. The device is used for patient treatment by prescription only and is intended to be used in the home under the supervision of a caregiver during periods of sleep.

ADDRESSING UNMET NEED: Non-drug option for treatment of ADHD in pediatric patients through the use of mild nerve stimulation, a first of its kind

GENERIC DEVICE TYPE:Transcutaneous electrical nerve stimulator for Attention Deficit Hyperactivity Disorder

  • Prescription device that stimulates transcutaneously or percutaneously through electrodes placed on the forehead


  • Cell-phone sized device generates low-level electrical pulse and connects via wire to a small patch that adheres to a patient’s forehead
  • Delivers low-level electrical stimulation to branches of trigeminal nerve, which sends therapeutic signals to the parts of the brain involved in ADHD
  • Neuroimaging studies show that eTNS increases activity in brain regions that are known to be important in regulating attention, emotion and behavior


  • Clinical trial, n=62 children with moderate to severe ADHD, eTNS vs. placebo
  • Primary endpoint: Improvement on clinician-administered ADHD Rating Scale, ADHD-RS
  • Subjects using eTNS device had statistically significant improvement in ADHD symptoms vs. placebo group
  • At end of week four, the average ADHD-RS score in eTNS decreased from 34.1 to 23.4 points, versusdecrease from 33.7 to 27.5 points in placebo
  • Most common side effects: Drowsiness, an increase in appetite, trouble sleeping, teeth clenching, headache and fatigue; no serious adverse events 

IDENTIFIED RISKS: Adverse tissue reaction, Injury or discomfort from electrical stimulation, including burns and nerve damage, Misuse that may result in device failure, user discomfort, or injury, Skin irritation or infection from use on broken skin 


  • Regulation:21 CFR 882.5898
  • Regulation Name: Transcutaneous electrical nerve stimulator for Attention Deficit Hyperactivity Disorder
  • Regulatory Class: Class II
  • Product Code: QGL




Xvivo Perfusion Inc. 

INDICATION FOR USE: For use in flushing and temporary continuous normothermic machine perfusion of initially unacceptable excised donor lungs during which time the ex-vivo function of the lungs can be reassessed for transplantation.


  • Lung transplantation is life-saving treatment for end-stage lung disease
  • Many patients die while waiting for suitable lungs for transplant
  • Only 15 percent of lungs from deceased donors suitable for transplantation
  • New device to temporarily ventilate, oxygenate, and perfuse preservation solution through lungs that were initially thought to be unacceptable for transplant


  • Consists of XPS Perfusion Cart Hardware, fluid path and non-fluid path disposables, XPS Cart Software, and STEEN Solution
  • STEEN Solution™ is clear, sterile, non-pyrogenic, non-toxic physiological salt solution containing human serum albumin (HSA) and dextran 40
  • Extracellular (low potassium) electrolyte solution with physiological colloid-osmotic pressure (COP) designed for use as a temporary continuous normothermic machine perfusion solution for ex vivo assessment of isolated lungs after removal from the donor


  • Study involving 332 sets of donor lungs allocated into three groups
  • Control group: Lungs initially deemed suitable for transplant that were provided to 116 recipients after standard preservation
  • Second group: Lungs initially deemed unsuitable for transplant and, after being perfused with the Xvivo Perfusion System, were implanted into 110 recipients
  • Third group: Perfused with the Xvivo Perfusion System and were still deemed not suitable after the perfusion, and therefore were not implanted into patients
  • One-year survival rate: 94% (Control) vs 86.4% (Second and third groups)
  • Difference in rates was not deemed to be clinically significant
  • Most common adverse events: Acute rejection, bronchial complications, respiratory failure and infections


  • Classification: III
  • Procode: PHO
  • Originally granted marketing authorization in 2014 under humanitarian device exemption (HDE), limiting use to maximum of 8,000 patients per year
  • PMA pathway allows increased number of lungs to be available for transplant
  • Post-Approval requirements: Long-Term Post Approval Studies



COMANECI Embolization Assist Device

Rapid Medical

INDICATION FOR USE: For use in the neurovasculature as a temporary endovascular device used to assist in the coil embolization of wide-necked intracranial aneurysms with a neck width ≤ 10 mm. A wide-necked intracranial aneurysm defines the neck width as ≥ 4 mm or a dome-to-neck ratio < 2

GENERIC TYPE OF DEVICE: Temporary coil embolization assist device

  • Prescription device intended for temporary use in the neurovasculature to  mechanically assist in the embolization of intracranial aneurysms with embolic coils. The device is delivered into the neurovasculature with an endovascular approach. This device is not intended to be permanently implanted and is removed from the body when the procedure is completed.


  • Infection: Sterilization validation, Pyrogenicity testing, Shelf life testing, Labeling
  • Adverse tissue reaction: Biocompatibility evaluation
  • Tissue or vessel damage: Non-clinical performance testing, Clinical performance testing, Labeling
  • Thromboembolic event:  Non-clinical performance testing, Clinical performance testing, Labeling
  • Coils ensnarement: Non-clinical performance testing, Clinical performance testing, Labeling


  • Regulation Number: 21 CFR 882.5955
  • Regulation Name: Temporary coil embolization assist device
  • Regulatory Class: Class II
  • Product Code: PUU




Theranica Bioelectronics ltd

INDICATION FOR USE: For acute treatment of migraine with or without aura in patients 18 years of age or older who do not have chronic migraine. It is a prescription use, self-administered device for use in the home environment at the onset of migraine headache or aura.

GENERIC DEVICE TYPE: Trunk and limb electrical stimulator to treat headache

  • Device intended to treat headache through the application of electrical stimulation anywhere on the body of the patient apart from the patient’s head or neck through electrodes placed on the skin. The stimulation may be provided transcutaneously or percutaneously


  • Adverse tissue reaction: Biocompatibility evaluation
  • Electrical, mechanical, or thermal hazards that may result in user discomfort or injury: Non-clinical performance testing, Electrical, mechanical, and thermal safety testing, Electromagnetic compatibility (EMC) testing, Software verification, validation, and hazard analysis, Labeling
  • Interference with other devices: Electromagnetic compatibility (EMC) testing, Labeling
  • Software malfunction leading to injury or discomfort: Software verification, validation, and hazard analysis
  • Hardware malfunction leading to injury or discomfort: Non-clinical performance testing, Shelf life testing, Labeling
  • Use error that may result in user discomfort, injury, or delay treatment for headaches: Labeling


  • Regulation Number: 21 CFR 882.5899
  • Regulation Name: Trunk and limb electrical stimulator to treat headache
  • Regulatory Class: Class II
  • Product Code: QGT



ZIKV Detect 2.0 IgM Capture ELISA


INDICATION FOR USE: Intended for the qualitative detection of Zika virus IgM
antibodies in human sera for the presumptive clinical laboratory diagnosis of Zika virus infection.
The assay is intended for use only in patients with clinical signs and symptoms consistent with Zika virus infection, and/or CDC Zika virus epidemiological criteria (e.g., history of residence in or travel to a geographic region with active Zika transmission at the time of travel, or other epidemiological criteria for which Zika virus testing may be indicated). Assay results are for the presumptive detection of IgM antibodies to Zika virus (ZIKV). Positive results must be confirmed by following the latest CDC guidelines for the diagnosis of Zika virus infection.


  • 1st Commercial serology kit to receive FDA Marketing Authorization
  • Previous tests for detecting Zika virus IgM antibodies—including the ZIKV Detect 2.0 IgM Capture ELISA—had been authorized only for emergency use under the FDA’s Emergency Use Authorization (EUA) authority

GENERIC DEVICE TYPE: Zika virus serological reagents

  • In vitro diagnostic devices that consist of antigens or antibodies for the detection of Zika virus or Zika antibodies in human specimens from individuals who have signs
    and symptoms consistent with Zika virus infection and/or epidemiological risk factors. The detection aids in the diagnosis of current or recent Zika virus infection or serological status. Negative results obtained with this test do not preclude the possibility of Zika virus infection, past or present. Positive results should be interpreted with consideration of other clinical information and laboratory findings and should not be used as the sole basis for treatment or other patient management decisions.


  • Risk of false results: Device description, performance characteristics, validation procedures, labeling
  • Failure to correctly interpret test results: Device description, performance characteristics, Labeling
  • Failure to correctly operate the device: Device description, performance characteristics, validation procedures, Labeling

REGULATORY PATHWAY: De Novo request (previously authorized via EUA)

  • Regulation Number: 21 CFR 866.3935
  • Regulation Name: Zika Virus Serological Reagents
  • Regulatory Class: Class II
  • Product Code: QFO


Image credits: NeuroSigma, Xvivo, Rapid Medical, Theranica, InBios

Drug and Vaccine Authorizations: EVENITY for osteoporosis, DENGVAXIA for Dengue, MAVYRET for Hep C in children, BENLYSTA in SLE, TIBSOVO for AML, VYNDAQEL/VYNDAMAX for cardiomyopathy, RUZURGI for LEMS


EVENITY (romosozumab-aqqg) injection, for subcutaneous use 


INDICATION FOR USE: Treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy
Limitations of Use : Anabolic effect wanes after 12 monthly doses of therapy. Therefore, the duration of EVENITY use should be limited to 12 monthly doses. If osteoporosis therapy remains warranted, continued therapy with an anti-resorptive agent should be considered

  • > 10 million US women osteoporosis; weakened bones likely to fracture
  • Approval provides women with postmenopausal osteoporosis with high risk of fracture with a new treatment

MECHANISM OF ACTION: Monoclonal antibody that inhibits action of sclerostin, a regulatory factor in bone metabolism; increases bone formation and, to a lesser extent, decreases bone resorption

  • 2 randomized, double-blind studies, placebeo and alendronate controlled respectively, n>11,000 women with postmenopausal osteoporosis
  • Endpoints: Risk of a new fracture in spine (vertebral fracture): 73% lowered risk vs. placebo, maintained over the second year of trial when Evenity.  50% lowered risk vs. two years of alendronate alone
  • Evenity followed by alendronate reduced risk of fractures in other bones (nonvertebral fractures) vs. alendronate alone
  • Boxed Warning: Potential risk for myocardial infarction, stroke and cardiovascular death
  • Common side effects: Joint pain, headache, injection site reactions
  • Pediatric assessments: Waived; do not apply to population
  • Postmarketing requirements: Cardiovascular safety



DENGVAXIA (Dengue Tetravalent Vaccine, Live) Suspension for Subcutaneous Injection

Sanofi Pasteur

INDICATION FOR USE: indicated for the prevention of dengue disease caused by dengue virus serotypes 1, 2, 3 and 4. DENGVAXIA is approved for use in individuals 9 through 16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas
Limitations of use: Not approved for use in individuals not previously infected by any dengue virus serotype or for whom this information is unknown; Safety and effectiveness have not been established in individuals living in dengue non-endemic areas who travel to dengue endemic areas


  • FDA committed to working with CDC and WHO to combat public health threats
  • Approval is important step toward reducing impact of virus in endemic US regions

MECHANISM OF ACTION: Elicits dengue-specific immune responses against four dengue virus serotypes


  • Three randomized, placebo-controlled studies, n=35,000 individuals in dengue-endemic areas, including Puerto Rico, Latin America and Asia Pacific region, 9-16 years of age
  • Endpoint: Symptomatic virologically-confirmed dengue (VCD); DENGVAXIA 76%  effective in preventing VCD in individuals who previously had laboratory- confirmed dengue disease


  • Most commonly reported side effects: Headache, muscle pain, joint pain, fatigue, injection site pain and low-grade fever


  • Priority Review and a Tropical Disease Priority Review Voucher
  • Postmarketing Study Requirement/Commitments: Safety and effectiveness in children 2 to < 9 years of age



MAVYRET (glecaprevir and pibrentasvir) tablets


INDICATION FOR USE: Treatment of adult and pediatric patients 12 years and older or weighing at least 45 kg with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A)

ADDRESSING UNMET NEED:  First treatment for all genotypes of hepatitis C in pediatric patients

MECHANISM OF ACTION: Fixed-dose combination of glecaprevir and pibrentasvir, which are direct-acting antiviral agents against the hepatitis C virus


  • Open-label study, n=47  adolescent subjects 12 -< 18 years  with genotype 1, 2, 3 or 4 HCV infection without cirrhosis or with mild cirrhosis, 8 or 16 weeks.
  • 100% had no virus detected in blood 12 weeks after finishing treatment, suggesting  infection had been cured


  • Adverse reactions observed were consistent with those observed in adults
  • Most commonly reported adverse reactions: Headache and fatigue


  • Initial US approval (NDA) in adult patients in 2017



BENLYSTA (belimumab) intravenous infusion


INDICATION FOR USE: Treatment of patients aged 5 years and older with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy


  • First treatment for pediatric patients with Systemic Lupus Erythematosus (SLE)
    • Benlysta has been approved for use in adult patients since 2011


  • International, randomized, doubleblind, placebo-controlled, 5