1. Pediatric Clinical investigator training workshop
Susan McCune, M.D.
Director, OPT, OC/FDA
Welcome and Introduction
February 28, 2019

2. Disclaimer
The views presented here are personal and do not necessarily reflect the views of the Agency
All specific drug development questions should be discussed with the relevant review division

3. Drug Development Overview
Nwaka S and Ridley RG. Virtual drug discovery and development for neglected diseases through public-private partnerships. Nat. Rev. Drug Discov. 2: , 2003

4. Need For Collaboration
Nwaka S and Ridley RG. Virtual drug discovery and development for neglected diseases through public-private partnerships. Nat. Rev. Drug Discov. 2: , 2003

5. Pediatric Historical Milestones and Legislation
1962 The FD&C Act amended: Drugs not tested in children should not be used in children
1974 AAP Committee on Drugs issues guidelines for evaluating drugs for pediatric use
1977 AAP issues guidelines for ethical conduct in pediatric studies
1979 FDA requires sponsors to conduct pediatric clinical trials before including pediatric information in the labeling
1992 Agency proposed Pediatric Labeling Rule and proposes extrapolation of efficacy from other data
1994 Final Rule on Pediatric Labeling. Formalizes Extrapolation of Efficacy; manufacturers to update labeling if pediatric data existed; HOWEVER, it allowed a disclaimer to the labeling for drugs not evaluated in children
1994 Pediatric Plan to encourage voluntary development of pediatric data
1997 FDAMA creates pediatric exclusivity provision (voluntary), provides 6-month exclusivity incentive
1998 Pediatric Rule (mandatory): products are required to include pediatric assessments if the drug is likely to be used in a ‘‘substantial number of pediatric patients’’ (50,000) or if it may provide a ‘‘meaningful therapeutic benefit’’
2002 Pediatric Rule declared invalid by DC Federal Court; the rule exceeded FDA’s authority
2002 FDAMA reauthorized as BPCA. Maintains 6-month exclusivity added to patent life of the active moiety. Creates Office of Pediatric Therapeutics (including ethicist). Mandates pediatric focused safety reviews
2003 PREA re-establishes many components of the FDA’s 1998 pediatric rule. Orphan products are exempted
2007 FDAAA Reauthorizes BPCA & PREA for 5 years. Pediatric Review Committee (PeRC) formed. Studies submitted will result in labeling. Negative and positive results of pediatric studies will be placed in labeling
2012 FDASIA legislation makes permanent BPCA and PREA

6. PREA vs. BPCA PREA BPCA Drugs and biologics Required studies
Studies may only be required for approved indication(s)
Products with orphan designation are exempt from requirements*
Pediatric studies must be labeled
Drugs and biologics
Voluntary studies
Studies relate to entire moiety and may expand indications
Studies my be requested for products with orphan designation
Pediatric studies must be labeled
* RACE for Children Act – Elimination of orphan exemption from pediatric studies for cancer drugs directed at relevant molecular targets

7. NICHD BPCA
For the NIH to prioritize therapeutic areas and sponsor clinical trials and other research about on- and off-patent drug products that need further study in children

8. NICHD BPCA
More than 100 drugs/therapeutics and 46 conditions/indications prioritized for further study
More than 30 clinical trials funded to improve the knowledge of medicines used in children
BPCA activities have resulted in 7 labeling changes
In 2018, Pediatric Trials Network (PTN) at the Duke Clinical Research Institute received an 8 year grant for $96 million
Focus on breastfeeding women and mental health for children
Over the previous 8 years (given $95 million in 2010)
26 clinical trials in 13 different therapeutic areas
Enrolling over 8,000 children
Focus on neonatal and obesity trials

9. BPCA/PREA Pediatric Labeling Changes 1998-2017

10. BPCA/PREA Pediatric Labeling Changes 1998 – 6/2018

11. Drug Development Paradigm

12. Pediatric Drug Labels Impact to Patients Clinical Trials
Innovative Designs
Biomarkers
Clinical Outcome
Assessment Tools
Network Sites
Basic Science Research
Natural History
Pathophysiology of Disease
Ontogeny of Metabolic Pathways
Micro-assays
Definition of Endpoints
Clinically Meaningful
Short Term/Long Term
Safety Assessments
Consortia
Leverage Insights
Academia
Government
Industry
Patient Advocacy Groups
Modeling and Simulation
Ontogeny of Metabolic Pathways
PK-PD Studies
IT Delivery Systems
Interoperable Systems
Standardized Data
Standardized Case Report Forms
Impact to Patients
Better Dosing
More Appropriate Use of Current Drugs
Increased Access to New Drugs
Pediatric Drug Labels

13. Workshop Agenda Setting the Stage Hot Topics The Basics
Funding and Engagement
Practical Applications

14. Office of Pediatric Therapeutics
To contact us:
Susan McCune, M.D.
Office of Pediatric Therapeutics
OC/FDA