Global Pediatric Development of Drugs, Biologics, and Medical Devices
115
and approaches to potentially support increased
pediatric development opportunities.
Benefits
Unlike other major region regulatory bodies,
Japan has implemented sponsor incentives to
improve pediatric drug development. Table 10-3
provides a timeline of key Japan pediatric devel-
opment incentives. Two key incentives include
extending the re-examination period and provid-
ing premium reimbursement pricing associated
with approved pediatric indications.
In Japan, the re-examination period is a
unique market exclusivity and data protection
system that serves as an incentive for drug
development sponsors. The system applies to new
chemical entities and drugs previously approved
for new clinical indications. Japanese regulators
re-examine the safety and efficacy of drugs follow-
ing approval in view of the data collected during
the re-examination period.16,17 The re-examination
period can range from four to 10 years after drug
approval. The data submitted during the period is
not available to generic drug manufacturers. The
re-examination period mandate for pediatric drug
development is outlined in the Pharmaceutical
and Medical Safety Bureau (PMSB) Notification
No. 1324 “Concerning Enforcement of the Partial
Revision of the Ministerial Ordinance relating to
Good Post-Marketing Surveillance Practice and
Review of Post-Marketing Surveillance for Drug
Review” dated 27 December 2000. The re-exam-
ination period can be extended to 10 years if a
clinical trial is planned to study pediatric dosage
during or after marketing authorization applica-
tion of a drug.18
An additional incentive for pediatric drug
development in Japan is that a premium rate
is added to the reimbursement drug price for
approved products with pediatric dosage indi-
cations that describe use in the entire pediatric
patient population or specific age subsets.19 This
Table 10-2. Timeline of Key Initiatives
Supporting Pediatric Development in Japan
Initiative/Guidance Year
ICH E11 Pediatric Guidance adopted 2000
Council for Unapproved Drugs/
Indications Scheme 2010
PMDA Pediatric Drugs Working
Group 2011
Pharmaceutical Affairs Consultation
on R&D Strategy 2011
Figure 10-1. Japan Unapproved Drug Scheme Workflow
[Academia, patients group]
Submit requests on
unapproved/off-label use
[Pharmaceutical industry]
Conduct development for
marketing authorization Study Group on
Unapproved and
Off-label Drugs of
High Medical Need
7 Working Groups
[Government]
Provide support through
• Designation of orphan
medicinal products
• Validation of public
knowledge-based
application
• Validation of necessary
test for market application
[Related academia,
pharmaceutical industry]
Submit its opinion
Submit requests/gather
information on applicability Evaluate medical need Develop the product
Source: Hirata M. Pediatric Drug Development in Japan and International Regulatory Collaboration. 14th DIA Japan
Annual Meeting 2017.
115
and approaches to potentially support increased
pediatric development opportunities.
Benefits
Unlike other major region regulatory bodies,
Japan has implemented sponsor incentives to
improve pediatric drug development. Table 10-3
provides a timeline of key Japan pediatric devel-
opment incentives. Two key incentives include
extending the re-examination period and provid-
ing premium reimbursement pricing associated
with approved pediatric indications.
In Japan, the re-examination period is a
unique market exclusivity and data protection
system that serves as an incentive for drug
development sponsors. The system applies to new
chemical entities and drugs previously approved
for new clinical indications. Japanese regulators
re-examine the safety and efficacy of drugs follow-
ing approval in view of the data collected during
the re-examination period.16,17 The re-examination
period can range from four to 10 years after drug
approval. The data submitted during the period is
not available to generic drug manufacturers. The
re-examination period mandate for pediatric drug
development is outlined in the Pharmaceutical
and Medical Safety Bureau (PMSB) Notification
No. 1324 “Concerning Enforcement of the Partial
Revision of the Ministerial Ordinance relating to
Good Post-Marketing Surveillance Practice and
Review of Post-Marketing Surveillance for Drug
Review” dated 27 December 2000. The re-exam-
ination period can be extended to 10 years if a
clinical trial is planned to study pediatric dosage
during or after marketing authorization applica-
tion of a drug.18
An additional incentive for pediatric drug
development in Japan is that a premium rate
is added to the reimbursement drug price for
approved products with pediatric dosage indi-
cations that describe use in the entire pediatric
patient population or specific age subsets.19 This
Table 10-2. Timeline of Key Initiatives
Supporting Pediatric Development in Japan
Initiative/Guidance Year
ICH E11 Pediatric Guidance adopted 2000
Council for Unapproved Drugs/
Indications Scheme 2010
PMDA Pediatric Drugs Working
Group 2011
Pharmaceutical Affairs Consultation
on R&D Strategy 2011
Figure 10-1. Japan Unapproved Drug Scheme Workflow
[Academia, patients group]
Submit requests on
unapproved/off-label use
[Pharmaceutical industry]
Conduct development for
marketing authorization Study Group on
Unapproved and
Off-label Drugs of
High Medical Need
7 Working Groups
[Government]
Provide support through
• Designation of orphan
medicinal products
• Validation of public
knowledge-based
application
• Validation of necessary
test for market application
[Related academia,
pharmaceutical industry]
Submit its opinion
Submit requests/gather
information on applicability Evaluate medical need Develop the product
Source: Hirata M. Pediatric Drug Development in Japan and International Regulatory Collaboration. 14th DIA Japan
Annual Meeting 2017.