Marketing Authorizations: TALUS SPACER for ankle avascular necrosis, eXciteOSA for mild obstructive sleep apnea, COSELA for chemotherapy-induced myelosuppression

Patient Specific TALUS SPACER

Additive Orthopaedics, LLC.

INDICATION FOR USE: For avascular necrosis (AVN)of the ankle joint

The anatomical landmarks necessary for the design and creation of the Spacer must be present and identifiable on computed tomography scan


  • AVN is a rare condition that causes the death of bone tissue due to lack of blood supply
  • Implant provides joint-sparing alternative to other surgical interventions commonly used in late-stage AVN


  • Solid, polished replica of the patient’s bone to allow patient to regain motion and reduce pain without amputation
  • Implant is 3D printed in CoCr using a laser sintering platform
  • All surfaces of the device are hand polished to a mirror finish
  • Implant is cleaned and passivated per ASTM A967 and will be sterilized by the end user via steam sterilization.
  • Creation of a patient-specific device is achieved via computed tomography (CT) scanning and CAD/CAM generation
  • No specific instruments are provided with the subject device


  • 31 patients and 32 talus replacement surgeries (one patient had operations on both ankles) with the implant
  • Primary probable benefit endpoint: Reduction in baseline level pain following surgery using the Visual Analog Scale (“VAS”) for pain; secondary endpoints of ankle range of motion, Foot and Ankle Outcome Scores
  • Improvement in scores after surgery with further improvement 2 and 3 years after surgery
  • Few safety events : Pain and scare tissue; most significant risk is reoperation

REGULATORY PATHWAY: Humanitarian Device Exemption

  • Humanitarian Use Designation (HUD); intended to benefit patients for condition that affects not more than 8,000 individuals in the U.S. per year
  • Post-Approval Study (PAS) is a prospective post-approval US registry study to provide ongoing safety and probable benefit assessment



Signifier Medical Technologies, LLC.

INTENDED USE: For the reduction of snoring and obstructive sleep apnoea by strengthening tongue muscles via electrical muscle stimulation

INDICATIONS FOR USE: For use to reduce snoring and mild sleep apnoea (AHI<15) for patients that are 18 years or older


  • OSA has potential serious long-term effects such as heart attack, glaucoma, diabetes, cancer and cognitive and behavioral disorders
  • First device used while awake that is intended to improve tongue muscle function, which in time can help prevent the tongue from collapsing backwards and obstructing the airway during sleep


  • Removable tongue muscle stimulation device that delivers neuromuscular stimulation to the tongue
  • Through a mouthpiece that sits around the tongue; has four electrodes, two located above the tongue and two located below the tongue
  • Provides electrical muscle stimulation action in sessions that consist of a series of electrical pulses with rest periods in between
  • Used for 20 minutes once a day during a wakeful state, for a period of 6‐weeks, and once a week thereafter


  • Clinical study, n= 115 patients with snoring, including 48 patients with snoring and mild OSA
  • Endpoint: 20% time reduction in snoring at levels > 40dB in 87 patients, 48% reduction in Apnea-Hypopnea Index in 41 patients with OSA
  •  Most common adverse events: Excessive salivation, tongue or tooth discomfort, tongue tingling, dental filling sensitivity, metallic taste, gagging and tight jaw
  • Patients should receive a comprehensive dental examination prior to use of the device

REGULATORY PATHWAY: De Novo classification


COSELA (trilaciclib) injection

G1 Therapeutics

INDICATION FOR USE: To decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan containing regimen for extensive-stage small cell lung cancer (ES-SCLC)


  • Protecting bone marrow function may help make their chemotherapy for ES-SCLC safer and improve treatment compliance
  • Treatment option can reduce the occurrence of a common, harmful side effect of chemotherapy

MECHANISM OF ACTION: Transient inhibitor of CDK 4 and 6. Hematopoietic stem and progenitor cells
(HSPCs) in the bone marrow give rise to circulating neutrophils, RBCs, and platelets. HSPC proliferation is dependent on CDK4/6 activity


  • Three randomized, double-blind, placebo-controlled trials, n=245 patients, COSELA vs placebo
  • Primary endpoint: Proportion of patients with severe neutropenia and duration of severe neutropenia in the first cycle of chemotherapy
  • COSELA resulted in lower chance of severe neutropenia vs, placebo; also reduced duration of sever neutropenia
  • Most common side effects: Fatigue; low levels of calcium, potassium and phosphate; increased levels of an enzyme called aspartate aminotransferase; headache; and infection in the lungs (pneumonia)
  • Patients should also be advised about injection site reactions, acute drug hypersensitivity, interstitial lung disease/pneumonitis (lung tissue inflammation) and embryo-fetal toxicity


  • Priority Review and Breakthrough Therapy designations


Image credit: Additive Orthopaedics, Signifier Medical, G1 Therapeutics

News and Views: Novel device innovation, Alternative nonclinical testing, Technology Modernization Action Plan, CDRH regulatory science tools, Drug safety priorities, CDER ISTAND program

Novel Device Innovation Despite COVID-19 Challenges

FDA approved, cleared, or authorized (“authorized”) 132 novel medical devices in 2020 (vs. 29 novel devices authorized in 2010)

  • Novel devices include those brought to market through PMA, HDE De Novo pathways and only those 510(K) with Breakthrough designation. Also first-of-a-kind devices authorized under EUA authority
  • Devices have ‘new’ technology AND address an unmet need, or may be safer or more effective than currently available alternatives

Examples include:

  • Game-based digital therapeutic to improve attention function in children with ADHD
  • Anterior cruciate ligament (ACL) implant as an alternative to ACL reconstruction to treat ACL tears
  • Continuous renal replacement therapy device for a lower weight pediatric population
  • Liquid biopsy next-generation sequencing companion diagnostic test
  • Cardiac ultrasound software that uses artificial intelligence (AI) for quality diagnostic images 
  • Automated insulin delivery and monitoring system for use in young pediatric patients
  • High density lipoprotein plasma delipidation system to reduce coronary artery atheroma in certain adult patients
  • High intensity focused ultrasound (HIFU), magnetic-resonance guided, ablation system for osteoid osteomas
  • Several COVID-19 specific devices for diagnosing and testing


Advancing Alternative Methods for nonclinical testing

Development of new regulatory approaches that can help improve predictivity–and potentially replace, reduce and/or refine animal testing

  • Leveraging advances in systems biology, stem cells, engineered tissues, and mathematical modeling
  • Enhancing ability to predict risk and efficacy
  • Examples include Microphysiological System and Organ-on-a-chip


Technology Modernization Action Plan (TMAP) to Accelerate Regulatory Decisions

TMAP approach to the use of technology for review of medical product applications and create a nimble workforce – with 3 components:

  • Modernization of the FDA’s technical infrastructure and operations
  • Enhancing FDA’s capabilities to develop technology products
  • Communication and collaboration with external stakeholders to drive technological progress


CDRH Regulatory Science Tools to Help Assess New Medical Devices

Catalog of tools developed by CDRH Office of Science and Engineering Labs (OSEL) to help improve development and assessment of emerging medical technologies

  • Should be evaluated for suitability within specific context of use
  • Tool categories : Phantoms, Methods, Computational Models and Simulations


CDER Drug Safety Priorities

Report of CDER’s work to manage drug safety issues through modernized safety surveillance methods and innovative responses to safety concerns

  • Key safety-related milestones and accomplishments of 2020
  • Initiatives for promoting and protecting public health during the COVID-19 pandemic
  • Ongoing programs such as Adverse Event Reporting System, Sentinel System, and Safe Use Initiative
  • Ongoing activities to address the national opioid crisis, cancer-causing impurities in medicines, Drug Safety Communications tools


Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program

Use of Drug Development Tools (DDTs) -methods, materials, or measures- that have the potential to facilitate drug development

  • ISTAND Pilot Program to expand DDT types by encouraging development of DDTs that are out of scope for existing DDT qualification programs but may still be beneficial for drug development


  • Tools that may help enable remote or decentralized trials
  • ​Tools that may advance our understanding of drugs
  • Tools that leverage digital health technologies


Image credit: FDA

COVID-19 News: Janssen vaccine review, Impact of new virus variants, Bamlanivimab and Etesevimab for treatment, Convalescent Plasma EUA update

Advisory Committee Meeting to Discuss Janssen Biotech Vaccine

 Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Feb. 26, 2021

  • Discuss data submitted in support of safety and effectiveness for EUA for a COVID-19 vaccine
  • VRBPAC members are independent, scientific and public health experts who advise FDA on the safety and effectiveness data
  • Final EUA decision made by FDA


Medical Product Development to Address New Virus Variants

FDA actively assessing impact of new strains on safety and effectiveness of authorized products

  • Guided by prior experience with evolving infectious diseases e.g. Influenza, HIV
  • Communicating with medical product sponsors on impact of COVID-19 variants on their products
  • New therapeutics: Focus on expediting virus-targeting monoclonal antibodies
  • New diagnostics: Focus on  in silico monitoring to assess for mutations and impact



Eli LIlly

INDICATION: Treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age or older weighing at least 40 kilograms [about 88 pounds]) who test positive for SARS-CoV-2 and who are at high risk for progressing to severe COVID-19

The authorized use includes treatment for those who are 65 years of age or older or who have certain chronic medical conditions

MECHANISM OF ACTION: Monoclonal antibodies that are specifically directed against the spike protein of SARS-CoV-2, designed to block the virus’ attachment and entry into human cells; the mAbs to different but overlapping sites on the spike protein of the virus


  • Placebo-controlled clinical trial of patients with COVID-19 at high risk for disease progression
  • Single iv of mAbs significantly reduced COVID-19-related hospitalization and death during 29 days of follow-up vs. compared to placebo
  • Safety and effectiveness continue to be evaluated



Convalescent Plasma EUA updated to Reflect New Data

EUA revised to limit use of high titer COVID-19 convalescent plasma

  • For the treatment of hospitalized patients with COVID-19 early in the disease course
  • For hospitalized patients who have impaired humoral immunity and cannot produce an adequate antibody response
  • Plasma with low levels of antibodies has not been shown to be helpful in COVID-19
  • Transfusion of COVID-19 convalescent plasma in hospitalized patients late in the course of illness (e.g. following respiratory failure requiring intubation and mechanical ventilation) has not been associated with clinical benefit


Image credit: FDA