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Background Analysis: US FDA Advisory Committee to Review Pediatric Safety of Regulated Products; Discuss Use of Opioid-Containing Cough Suppressants – SEP 11-12, 2017 (PEDAC)


The US FDA has scheduled a meeting of the Pediatric Advisory Committee (PEDAC) for Monday and Tuesday, September 11-12, 2017.

On Monday, September 11, 2017, the Committee will discuss the use of prescription opioid products for the treatment of cough in pediatric patients.

On Tuesday, September 12, 2017, the Committee will discuss pediatric-focused safety reviews for certain products that are 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).

Day 1 – Pediatric Treatment of Cough

Regulatory Background

On August 21, 2017, FDA Commissioner Gottlieb announced the upcoming meeting and issued a statement to briefly highlight some of the Agency’s ongoing efforts to evaluate prescription opioids approved to treat cough in children. He noted the FDA’s action in April 2017 to require the labeling of codeine, one type of opioid, to include a contraindication against any use in children under the age of 12 years. Next, the FDA is seeking input from the Pediatric Advisory Committee regarding current practice for the treatment of cough in children and benefit-risk considerations of the opioid drug class, with a particular focus on hydrocodone and codeine. He stated, “The panel of independent experts will provide valuable input to help inform the agency’s decision-making processes related to these medications.”

In addition to the contraindication against the use of codeine, he referred to a meeting that was held in April 2017 involving representatives of the FDA, the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP) about the use of opioid cough suppressants. He noted that the discussion was focused on determining the right treatment based on the length and severity of the symptoms, as well as treating the cause of the symptoms, rather than just quieting the cough, and he added that “depending on the situation, representatives suggested that other medications or non-drug therapies may be more appropriate.”

Day 2 – Pediatric-Focused Safety Reviews

On the second day of the meeting, the Committee will discuss pediatric-focused safety reviews for certain products that are 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).

Product Background

The following products will be reviewed, listed by FDA Center, followed by the current indication for each product (as of August 23, 2017). Typically, the FDA reviews 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 (CDER)

a. ABILIFY (aripiprazole)

ABILIFY is an atypical antipsychotic. The oral formulations are indicated for:

·      Schizophrenia (14.1)

·      Acute Treatment of Manic and Mixed Episodes associated with Bipolar I (14.2)

·      Adjunctive Treatment of Major Depressive Disorder (14.3)

·      Irritability Associated with Autistic Disorder (14.4)

·      Treatment of Tourette’s disorder (14.5)

The injection is indicated for:

·      Agitation associated with schizophrenia or bipolar mania (14.6)

b. KEPPRA/KEPPRA XR (levetiracetam)

KEPPRA is indicated for adjunctive therapy in the treatment of:

·      Partial onset seizures in patients one month of age and older with epilepsy (1.1)

·      Myoclonic seizures in patients 12 years of age and older with juvenile myoclonic epilepsy (1.2)

·      Primary generalized tonic-clonic seizures in patients 6 years of age and older with idiopathic generalized epilepsy (1.3)

Center for Devices and Radiological Health

a. CONTEGRA Pulmonary Valved Conduit (humanitarian device exemption (HDE)

CONTEGRA Pulmonary Valved Conduit is indicated for correction or reconstruction of the Right Ventricular Outflow Tract (RVOT) in patients aged less than 18 years with any of the following congenital heart malformations: Pulmonary Stenosis, Tetralogy of Fallot, Truncus Arteriosus, Transposition with Ventricular Septal Defect (VSD), and Pulmonary Atresia. In addition, the conduit is indicated for the replacement of previously implanted, but dysfunctional, pulmonary homografts or valved conduits.

b. ENTERRA Therapy System (HDE)

ENTERRA Therapy System is indicated for use in the treatment of chronic, intractable (drug refractory) nausea and vomiting secondary to gastroparesis of diabetic or idiopathic etiology.


Pleximmune is a laboratory blood test that aids in the prediction of the risk of a transplant rejection, known as Acute Cellular Rejection (ACR), in patients under 21 years who have undergone liver or small bowel transplants.

d. ELANA Surgical Kit (HDE)

Elana Surgical Kit is indicated, when connected to the Spectranetics Xenon-Chloride Laser Model CVX-300, for creating arteriotomies during an intracranial vascular bypass procedure in patients 13 years of age or older with an aneurysm or a skull base tumor affecting a large (> 2.5 mm), intracranial artery that failed balloon test occlusion, cannot be sacrificed, or cannot be treated with conventional means due to local anatomy or complexity.

Regulatory Background - BPCA/PREA/PMDSIA


The reports on these products are mandated through the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA). The FDA oversees two major provisions of BPCA and PREA that allow them to require pediatric studies. 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) was 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. Since 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 U.S. House of Representatives (as H.R. 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 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 any 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

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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.