Chapter 10: Drug Development—Japan
114
access through expedited development of highly
needed drugs or drugs with new indications/dos-
ages, including pediatric use, not yet approved in
Japan but already approved and widely used in at
least one of six western countries. These countries
include Australia, Canada, France, Germany, the
UK, and the US.10
Under this scheme, pharmaceutical sponsors
receive requests to develop or submit a Japan
new drug application (JNDA) for designated
drugs and/or indications. Once submitted,
PMDA conducts an accelerated fast track JNDA
review. The agency can waive the requirement
for additional region-specific studies, if deemed
acceptable. Figure 10-1 provides Japan’s unap-
proved drug scheme workflow. Public knowledge
can serve as the basis for approval. The following
are examples of public knowledge that can be
considered:
• Clinical data submitted to support drug
approval in one of the six aforementioned
countries and (off-label) clinical use.
• Literature (major medical textbooks or
guidance documents) to support usage of the
drug.11
In November 2011, PMDA established the
Pediatric Drugs Working Group.12 As of 2014, it
was composed of 18 PMDA members, including
pediatricians, physicians, and pharmacists from
the Office of New Drugs and Office of Safety.
The objective of the group is to promote efforts
to encourage the pharmaceutical industry and
clinical investigators to develop medicinal
products for children. PMDA collaborates with
foreign regulatory agencies, including US FDA,
EU EMA, Health Canada (HC), and Australia’s
Therapeutics Goods Administration (TGA), to
discuss issues raised in precedented drug data
package reviews to establish more appropriate
strategies. Views and positions are then shared
internally within PMDA and exchanged exter-
nally with domestic stakeholders (e.g., medical
institutions, industry groups).13 Figure 10-2
outlines Japan’s pediatric drugs working group
stakeholder and process overview.
In July 2011, PMDA launched the
Pharmaceutical Affairs Consultation on Research
and Development (R&D) Strategy.14 It is focused
on promising “seed-stage” research or technologies
to achieve realization of innovative drugs, medical
devices, and cellular and tissue-based products
being developed by universities, research institu-
tions, and start-up companies. Advice is provided
on quality, nonclinical, and clinical challenges that
arise in earlier stages of development.15 Although
the initiative is not solely focused on pediat-
rics, one of its key goals is to help stakeholders
understand and appreciate pediatric-specific issues
Table 10-1. Comparison of Japan, US, and EU Pediatric Development Regulations
Japan US EU
Regulations
None • PREAa
• RACEb
• BPCAc
Mandatory
• Pediatric Regulation (2007)
• Regulation EC (1901/2006)
Regulatory
Obligations
None • PSP must be submitted by the end of a
Phase II study for adults (PREA)
• WR by FDA conducting a clinical trial
for drug development (optional)
• Pediatric investigation by the end of
a Phase I study in adults
• PIP submitted prior to completion of
human adult PK studies
Notes: Pediatric investigation plan (PIP), pharmacokinetic (PK), pediatric study plan (PSP), written request (WR)
a. Pediatric Research Equity Act (PREA) of 2003 amended the Federal Food, Drug, and Cosmetic Act to require license
applications for new drugs and biological products to assess such drug’s or product’s safety and effectiveness for
relevant pediatric subpopulations, including dosage.
b. Research to Accelerate Cures and Equity for Children Act (RACE) of 2017 amended the Federal Food, Drug, and Cosmetic
Act to require sponsors of certain drugs and biological products for adult cancer to assess the use of their medica-
tions in pediatric populations.
c. Best Pharmaceuticals for Children Act (BPCA) of 2002 provides an incentive of additional marketing exclusivity to
sponsors who voluntarily complete pediatric clinical studies outlined in a written request issued by FDA.
114
access through expedited development of highly
needed drugs or drugs with new indications/dos-
ages, including pediatric use, not yet approved in
Japan but already approved and widely used in at
least one of six western countries. These countries
include Australia, Canada, France, Germany, the
UK, and the US.10
Under this scheme, pharmaceutical sponsors
receive requests to develop or submit a Japan
new drug application (JNDA) for designated
drugs and/or indications. Once submitted,
PMDA conducts an accelerated fast track JNDA
review. The agency can waive the requirement
for additional region-specific studies, if deemed
acceptable. Figure 10-1 provides Japan’s unap-
proved drug scheme workflow. Public knowledge
can serve as the basis for approval. The following
are examples of public knowledge that can be
considered:
• Clinical data submitted to support drug
approval in one of the six aforementioned
countries and (off-label) clinical use.
• Literature (major medical textbooks or
guidance documents) to support usage of the
drug.11
In November 2011, PMDA established the
Pediatric Drugs Working Group.12 As of 2014, it
was composed of 18 PMDA members, including
pediatricians, physicians, and pharmacists from
the Office of New Drugs and Office of Safety.
The objective of the group is to promote efforts
to encourage the pharmaceutical industry and
clinical investigators to develop medicinal
products for children. PMDA collaborates with
foreign regulatory agencies, including US FDA,
EU EMA, Health Canada (HC), and Australia’s
Therapeutics Goods Administration (TGA), to
discuss issues raised in precedented drug data
package reviews to establish more appropriate
strategies. Views and positions are then shared
internally within PMDA and exchanged exter-
nally with domestic stakeholders (e.g., medical
institutions, industry groups).13 Figure 10-2
outlines Japan’s pediatric drugs working group
stakeholder and process overview.
In July 2011, PMDA launched the
Pharmaceutical Affairs Consultation on Research
and Development (R&D) Strategy.14 It is focused
on promising “seed-stage” research or technologies
to achieve realization of innovative drugs, medical
devices, and cellular and tissue-based products
being developed by universities, research institu-
tions, and start-up companies. Advice is provided
on quality, nonclinical, and clinical challenges that
arise in earlier stages of development.15 Although
the initiative is not solely focused on pediat-
rics, one of its key goals is to help stakeholders
understand and appreciate pediatric-specific issues
Table 10-1. Comparison of Japan, US, and EU Pediatric Development Regulations
Japan US EU
Regulations
None • PREAa
• RACEb
• BPCAc
Mandatory
• Pediatric Regulation (2007)
• Regulation EC (1901/2006)
Regulatory
Obligations
None • PSP must be submitted by the end of a
Phase II study for adults (PREA)
• WR by FDA conducting a clinical trial
for drug development (optional)
• Pediatric investigation by the end of
a Phase I study in adults
• PIP submitted prior to completion of
human adult PK studies
Notes: Pediatric investigation plan (PIP), pharmacokinetic (PK), pediatric study plan (PSP), written request (WR)
a. Pediatric Research Equity Act (PREA) of 2003 amended the Federal Food, Drug, and Cosmetic Act to require license
applications for new drugs and biological products to assess such drug’s or product’s safety and effectiveness for
relevant pediatric subpopulations, including dosage.
b. Research to Accelerate Cures and Equity for Children Act (RACE) of 2017 amended the Federal Food, Drug, and Cosmetic
Act to require sponsors of certain drugs and biological products for adult cancer to assess the use of their medica-
tions in pediatric populations.
c. Best Pharmaceuticals for Children Act (BPCA) of 2002 provides an incentive of additional marketing exclusivity to
sponsors who voluntarily complete pediatric clinical studies outlined in a written request issued by FDA.