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