Tarius SAC Tracker®


Background Analysis: US FDA Advisory Committee to Review Drug Products and Devices Under PREA/BPCA/PMDSIA – MAR 23, 2018 (PEDAC)


The US FDA has scheduled a meeting of the Pediatric Advisory Committee (PEDAC) for Friday, March 23, 2018. The Committee will discuss pediatric-focused safety reviews, as mandated by the Best Pharmaceuticals for Children Act (BPCA), the Pediatric Research Equity Act (PREA), and the Pediatric Medical Device Safety and Improvement Act (PMDSIA).

Note: On February 16, 2018, subsequent to publishing this report, the FDA announced the following additional meeting topics:

  • Update regarding labeling change for inhaled corticosteroid long-acting β-2 agonists (ICS/LABAs);
  • Safety labeling for gadolinium products;
  • Overview of the FDA Adverse Event Reporting System (FAERS) and reports on reduced or lack of efficacy for certain generic drugs; and
  • Generic drug approval process; and discussion on the differences in the approval process for brand name drugs versus generic drugs; exceptions.

Product Background

Products for review under BPCA/PREA/PMDSIA

The PEDAC will discuss pediatric-focused safety reviews for the products and devices listed below, by FDA Center, followed by the indication(s) for each (as of January 2, 2018). Typically, the FDA reviews the pediatric safety of these products, proposes how to continue surveillance, and asks the Committee to vote on whether they are in agreement with the FDA’s proposals.

Center for Drug Evaluation and Research

a)     BANZEL

BANZEL is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in pediatric patients 1 year of age and older and in adults.


INTUNIV is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications.

c)     LEXAPRO

1.1 Major Depressive Disorder

Lexapro (escitalopram) is indicated for the acute and maintenance treatment of major depressive disorder in adults and in adolescents 12 to 17 years of age [see Clinical Studies (14.1)].

A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation.

1.2 Generalized Anxiety Disorder

Lexapro is indicated for the acute treatment of Generalized Anxiety Disorder (GAD) in adults [see Clinical Studies (14.2)].

Generalized Anxiety Disorder (DSM-IV) is characterized by excessive anxiety and worry (apprehensive expectation) that is persistent for at least 6 months and which the person finds difficult to control. It must be associated with at least 3 of the following symptoms: restlessness or feeling keyed up or on edge, being easily fatigued, difficulty concentrating or mind going blank, irritability, muscle tension, and sleep disturbance.

Center for Devices and Radiological Health

a.     FLOURISH (Humanitarian Device Exemption (HDE))

The Flourish Pediatric Esophageal Atresia Device is indicated for use in lengthening atretic esophageal ends and creating an anastomosis with a non-surgical procedure in pediatric patients, up to one year of age with esophageal atresia without a tracheoesophageal fistula (TEF) or in pediatric patients up to one year of age for whom a concurrent TEF has been closed as a result of a prior procedure. This device is indicated for atretic segments < 4 cm apart.

b.     ACTIVA Deep Brain Stimulation (DBS) (HDE)


Bilateral stimulation of the internal globus pallidus (GPi) or the subthalamic nucleus (STN) using Medtronic DBS Therapy for Parkinson's Disease is indicated for adjunctive therapy in reducing some of the symptoms in individuals with levodopa-responsive Parkinson's disease of at least 4 years' duration that are not adequately controlled with medication, including motor complications of recent onset (from 4 months to 3 years) or motor complications of longer-standing duration.


Unilateral thalamic stimulation of the ventral intermediate nucleus of the thalamus (VIM) using Medtronic DBS Therapy for Tremor is indicated for the suppression of tremor in the upper extremity. The system is intended for use in patients who are diagnosed with Essential Tremor or Parkinsonian tremor not adequately controlled by medications and where the tremor constitutes a significant functional disability. The safety or effectiveness of this therapy has not been established for bilateral stimulation.


Medtronic DBS Therapy for Dystonia is indicated for unilateral or bilateral stimulation of the internal globus pallidus (GPi) or the subthalamic nucleus (STN) to aid in the management of chronic, intractable (drug refractory) primary dystonia, including generalized and/or segmental dystonia, hemidystonia, and cervical dystonia (torticollis), in patients 7 years of age or above.


The Medtronic Reclaim DBS Therapy is indicated for bilateral stimulation of the anterior limb of the internal capsule (AIC) as an adjunct to medications and as an alternative to anterior capsulotomy for treatment of chronic, severe, treatment-resistant obsessive-compulsive disorder (OCD) in adult patients who have failed at least three selective serotonin reuptake inhibitors (SSRIs).


The LIPOSORBER LA-15 System is indicated for use in the treatment of pediatric patients with nephrotic syndrome associated with primary focal segmental glomerulosclerosis (FSGS) when standard treatment options, including corticosteroid and/or calcineurin inhibitors treatments, are unsuccessful or not well tolerated, and the patient has a glomerular filtration rate (GFR) ≥ 60 ml/min/1.73m or when the patient is post-renal transplantation.


The Impella RP System is indicated for providing temporary right ventricular support for up to 14 days in patients with a body surface area ≥1.5 m2, who develop acute right heart failure or decompensation following left ventricular assist device implantation, myocardial infarction, heart transplant, or open-heart surgery.

Note: On February 16, 2018, subsequent to publishing this report, the FDA revised the list of CDRH products being reviewed at the meeting. They removed products a and d.

Regulatory Background - BPCA/PREA/PMDSIA

The reports on these products are mandated through the Best Pharmaceuticals for Children Act (BPCA), the Pediatric Research Equity Act (PREA), and the Pediatric Medical Device Safety and Improvement Act (PMDSIA).


BPCA and PREA were made permanent by the Food and Drug Administration Safety and Innovation Act (FDASIA) in 2012.

In 2003, PREA was first signed into law. It was reauthorized by the Food and Drug Administration Amendments Act (FDAAA) in 2007, and later made permanent with FDASIA in 2012. The Act requires pediatric studies and covers drugs, biologics, and medical products derived from living sources, such as vaccines, blood, and blood derivatives. Under the PREA, the FDA can require pediatric studies of a drug submitted in a new drug application if the FDA determines the product is likely to be used in a substantial number of pediatric patients, if the product would provide a meaningful benefit in the pediatric population over existing treatments, and absence of adequate labeling could pose a significant risk. At the same time, PREA does not delay the availability of drugs for adults. PREA does not apply to drugs that qualify for orphan drug designation or to generics.

In addition, the voluntary pediatric exclusivity provision of the Food and Drug Administration Modernization Act of 1997 (FDAMA) has been continued through BPCA since 2002.The Pediatric Exclusivity Provision of the BPCA allows companies to qualify for an additional six months of marketing exclusivity if they do the studies in children as requested by the FDA. Because the incentive under FDAMA did not apply to old antibiotics and other drugs that lack marketing exclusivity or patent protection, some categories of drugs have remained inadequately studied. For these products, BPCA provides a contract mechanism through the National Institutes of Health (NIH) to fund pediatric studies. In addition, if a company that has a drug with existing exclusivity or patent protection chooses not to conduct the requested pediatric studies, the FDA can refer the Written Request to the Foundation for the NIH to award grants so that third parties can conduct the needed studies.


The Pediatric Medical Device Safety and Improvement Act of 2007, which was passed on March 13, 2007 by the US House of Representatives (as HR 1494), did the following:

1) Amended the Federal Food, Drug, and Cosmetic Act to require an application for the approval of a medical device or a product development protocol to include: (1) a description of any pediatric subpopulations that suffer from the disease or condition that the device is intended to treat, diagnose, or cure; and (2) the number of affected pediatric patients.

2) Excluded a medical device distributed pursuant to the humanitarian device exemption from the prohibition that no device be sold for an amount that exceeds the cost of the device if: (1) the device is intended for the treatment or diagnosis of a disease or condition that occurs in pediatric patients; and (2) other specified requirements are met.

3) Required the Director of the National Institutes of Health (NIH) to designate a contact point to help innovators and physicians access funding for pediatric medical device development.

4) Required the Secretary of Health and Human Services (HHS) to award grants for demonstration projects to promote pediatric device development.

5) Included as a duty of the FDA’s Office of Pediatric Therapeutics increasing pediatric access to medical devices.

6) Allowed the Secretary of HHS to require: (1) postmarket surveillance on certain devices that are expected to have significant use in pediatric populations; and (2) a prospective surveillance period of more than 36 months for such devices, as necessary.

7) Required the HHS Secretary, acting through the Commissioner of the FDA, to establish a publicly accessible database of all studies and surveillance of medical devices.

What’s Next?

Tarius will send a Briefing Summary after briefing materials are posted to FDA’s website (typically within 2 days of the meeting). This report will provide a summary of the FDA and the Sponsor’s briefing materials.

Tarius will send a Results Wire soon after the meeting. This report will include the voting outcomes, if applicable, and key outcomes of the discussion.

METADATA: Sponsor: none Drug Name: several Drug Class: several Indication: pediatric uses

For more information about SAC Tracker reports and other benefits for our subscribers, click here.

DISCLAIMER: The information in this document is for informational purposes only. The SAC Tracker Background Analysis contains information from publicly available sources, including FDA, sponsor, scientific, and clinical websites. Tarius A/S assumes no liability for any inaccurate or incomplete information, or for any actions taken in reliance thereon. © Tarius A/S. All rights reserved.