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