46 Pharmaceutical Technology REGULATORY SOURCEBOOK MARCH 2021 P h a r mTe c h . c o m
tial adult authorization and the addition of pediatric la-
beling remains, approximately seven years on average (15).
The case studies described here demonstrate the practical
utility of the pediatric extrapolation framework to advance
and expedite pediatric drug development.
These case studies also exemplify how pre-competitive
efforts—leveraging data and knowledge exchange from
col laborat i ng pha rmaceut ica l compa nies, reg u lator y
agencies, and contract research organizations—contrib-
ute to the implementation and regulatory acceptance of
innovative and well-justified scientific approaches.
The PWG w it hin IQ-CPLG has leveraged its forum
to facilitate mu lti-sta keholder discussions to advance
t he t hi n k i ng on its appl icabi l it y i n moder n d r ug de-
velopment. Due to t he d iverse ex per t ise a nd perspec-
t ives of PWG members, t his for u m has helped foster
the evolution on the implementation of quantitative and
Bayesian approaches, and other methodologies for use
in pediatric ex trapolation. The inf luence ca n be seen
not only w it hin each member's respective compa nies
a nd t he i mpac t on ped iat r ic development pla ns, but
a lso on policy-ma k ing in globa l pharmaceutica l trade
organizations (European Federation of Pharmaceutical
Industries and Associations, Pharmaceutical Research
a nd Ma nu facturers of A merica, or Biotechnolog y In-
novation Orga nization) a nd decision-ma k ing at reg u-
lator y agencies (e.g., Entresto [sacubitril/valsartan] 2019 FDA
supplemental new drug application approval
for the treatment of
symptomatic heart failure with systemic left ventricular
systolic dysfunction in pediatric patients aged one year
and older) (16).
Importantly, the International Council for Harmoni-
zation (ICH) is working toward a global consensus guideline
intended to provide detailed guidance (17) on the use of
pediatric extrapolation to support successful acceleration
of marketing authorizations. Some members of the PWG
have overlapping roles in the pediatric extrapolation ICH
E11A expert work group and have been able to leverage
and incorporate consistency to what is expected to be an
inf luential international consensus guidance.
It is the authors' perspective that the IQ CPLG PWG
has played a crucial role in facilitating information shar-
ing and inf luence on the applicability and appropriate-
ness of the pediatric extrapolation framework, which has
the potential to hasten access of medicines to children.
References
1. H. Sun, et al., Ther Innov & Regul Sci. 1-7 (Aug. 18, 2017).
2. EMA, EMA Public Workshop on Extrapolation of Efficacy and
Safety in Medicine Development (London, 2016).
3. ICH, E11(R1) Guideline on Clinical Investigation of Medicinal
Products in the Pediatric Population, Step 5 version (2017).
4. AAP, "Update: Anti-Epileptic Drug Efficacy In Adults Can Be
Extrapolated to Pediatric Patients," (April 6, 2016).
5. IQ consortium CPLG PWG and ASCPT: "Challenges and Op-
portunities in Extrapolation," Pre-conference at ASCPT meet-
ing (March 21, 2018).
6. IQ Consortium "Strategies to Address Opportunities in Oncol-
ogy Pediatric Drug," Webinar (Dec. 19, 2018).
7. IQ Consortium and M-CERSI, "Pediatric Formulation Develop-
ment: Challenges of Today and Strategies for Tomorrow,"
Workshop (Baltimore, Md, Jun. 18–19, 2019).
8. J. S. Barrett, et al., Clin Pharmacol Ther 103 (3) 419–433 (2018).
9. J. S. Barrett, et al., Clin Pharmacol Ther 108 (1) 29–39 (2020).
10. M. Roth-Cline et al., "Ethical Considerations in Conducting Pe-
diatric Research" in Pediatric Clinical Pharmacology, H. W. Sey-
berth, A. Rane and M. Schwab, 219–244 (Springer, Berlin, Hei-
delberg, 2011).
11. E. G. Yan and K. M. Munir, Ethics and Behavior, 14 (1) 31-49
(2010).
12. X. Wang, A. Bello, and A. Roy. J Pharmacokinet Pharmacodyn
44, 11–143 (2017).
13. L. Gore, et al., J Clin Oncol 36 (13)1330–1338 (2018).
14. S. Vaidhyanathan et al., J Pharm Sci 108 (1) 741–749 (2019).
15. C. Bucci-Rechtweg, Clinical Ther 39 (10) 1920-2932 (2017).
16. Novartis, "Novartis Entresto Receives FDA Approval for Pedi-
atric Heart Failure, Helping to Address Critical Unmet Need for
Treatment Options," Press Release, Oct. 01, 2019, .
17. ICH, "Final Concept Paper Pediatric Extrapolation," Endorsed
by the Management Committee Oct. 17, 2017.
PT
About the authors
Sebastian Haertter*, sebastian.haertter@boehringer-ingel-
heim.com, is clinical pharmacology expert (director) trans-
lational medicine and clinical pharmacology, Boehringer
Ingelheim; S. Y. Amy Cheung is senior director, Certara;
Angela James is director, Astellas Pharma Global Develop-
ment; Ashley Strougo is head of M&S Germany, pharmaco-
kinetics, dynamics and metabolism, translational medicine,
Sanofi; Christina Bucci-Rechtweg is global head, pediatric
and maternal health policy, Novartis Pharmaceuticals Cor-
poration; Jing Liu is senior director, clinical pharmacology,
Pfizer; Meina Tao Tang is principal scientist, clinical phar-
macology, Genentech, Inc.; Paulien Ravenstijn is senior
consultant, qPharmetra LLC; Raafat Bishai is global clin-
ical program lead, AstraZeneca; Satyendra Suryawanshi
is director, clinical pharmacology and pharmacometrics,
Bristol Myers Squibb; and Solange Corriol-Rohou is se-
nior regulatory affairs and policy director for Europe, CMO
office and chair of AZ Paediatric Work Group Regulatory
Excellence, AstraZeneca; all authors are members of the IQ
Consortium.
*To whom all correspondence should be addressed.
Quality Collaboration
Extrapolation supported
the successful approval of
a pediatric indication for
dasatinib and informed
dosing and posology.
