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Chapter 15: Global Regulatory Strategy
jurisdiction that has adopted ICH guidelines also
has developed specific Module 1 guidance.
ICH publishes structure and content guide-
lines for Modules 2–5.
Module 2 contains summaries of the organi-
zation’s position on available data and summaries
of quality (QOS), safety (CSS, NCO) and effi-
cacy (CSE, CO). Regulators require the sponsor
to provide its assessment of the product’s overall
benefit-risk balance in this section, including any
outstanding uncertainty in either risk or benefit
at the time of initial regulatory review.
Module 3 provides information related to
how the product was developed, how it is man-
ufactured, evidence of product stability under
standard and stressed storage conditions and data
ensuring it can be manufactured reproducibly
and analyzed to generate a reproducible product
meeting an appropriate release specification.
Module 4 provides information related to
completed nonclinical analyses.
Module 5 provides the sponsor’s clinical trial
study reports demonstrating a tolerable safety
profile and positive beneficial effect.
ICH also has authored guidelines (quality,
safety and efficacy) clarifying expectations for the
information these sections should contain.
For a global organization, the goal is to gen-
erate a core regulatory dossier efficiently that can
be reused in multiple markets where it may wish
to register the product. Generating this dossier,
therefore, may take some regional differences and
requirements across markets into account. For
example, the core quality section may describe
process information related to a range of man-
ufacturing facilities supplying several markets,
allowing this information to be selected for the
relevant local dossier.
A regulatory professional has multiple roles
in generating the regulatory dossier:
• advising on content requirements
• ensuring coordinated delivery of multi-
ple components
• ensuring a balanced benefit-risk
assessment that acknowledges product
weaknesses and uncertainty, allowing
regulatory reviewers to focus on the
product’s key outstanding issues
• ensuring the messages delivered are
simple, clear and succinct to aid the
agency’s regulatory review and decrease
agency questions
Organizations generate the filing documents
required to complete each CTD section, but
following initial approval, may need to modify
specific sections using a variation, amendment or
supplement. For example, additional clinical data
may be generated with the intent of expanding
the product’s use, and the sponsor will be required
to provide a new clinical study report (CSR) and
proposed label changes to support the new use.
Companies often initially generate an ICH-
style dossier first and use this to generate the
dossiers for non-ICH countries.
Regional Dossiers
The dossier’s content and structure may need to
be modified to meet each regulatory authority’s
requirements in the region or country in which
the organization wishes to register the product.
This may include a range of additional consider-
ations. Some examples are provided below, and
specific requirements are called out at a high
level in Table 15-2.
• Providing extra data—some regulatory
agencies require additional clinical
data representing the local population,
e.g., China, Japan, etc., or data with an
alternative comparator representing that
market’s standard of care.
• Additional declarations—legal letters of
authority, Certificates of Analysis, exe-
cuted batch manufacturing records all are
examples of country-specific additions.
• Local forms—application forms, local
language versions of clinical summa-
ries, Certificates of Pharmaceutical
Product (CPPs) confirming prior
approval in another jurisdiction (typi-
cally US or EU).
Chapter 15: Global Regulatory Strategy
jurisdiction that has adopted ICH guidelines also
has developed specific Module 1 guidance.
ICH publishes structure and content guide-
lines for Modules 2–5.
Module 2 contains summaries of the organi-
zation’s position on available data and summaries
of quality (QOS), safety (CSS, NCO) and effi-
cacy (CSE, CO). Regulators require the sponsor
to provide its assessment of the product’s overall
benefit-risk balance in this section, including any
outstanding uncertainty in either risk or benefit
at the time of initial regulatory review.
Module 3 provides information related to
how the product was developed, how it is man-
ufactured, evidence of product stability under
standard and stressed storage conditions and data
ensuring it can be manufactured reproducibly
and analyzed to generate a reproducible product
meeting an appropriate release specification.
Module 4 provides information related to
completed nonclinical analyses.
Module 5 provides the sponsor’s clinical trial
study reports demonstrating a tolerable safety
profile and positive beneficial effect.
ICH also has authored guidelines (quality,
safety and efficacy) clarifying expectations for the
information these sections should contain.
For a global organization, the goal is to gen-
erate a core regulatory dossier efficiently that can
be reused in multiple markets where it may wish
to register the product. Generating this dossier,
therefore, may take some regional differences and
requirements across markets into account. For
example, the core quality section may describe
process information related to a range of man-
ufacturing facilities supplying several markets,
allowing this information to be selected for the
relevant local dossier.
A regulatory professional has multiple roles
in generating the regulatory dossier:
• advising on content requirements
• ensuring coordinated delivery of multi-
ple components
• ensuring a balanced benefit-risk
assessment that acknowledges product
weaknesses and uncertainty, allowing
regulatory reviewers to focus on the
product’s key outstanding issues
• ensuring the messages delivered are
simple, clear and succinct to aid the
agency’s regulatory review and decrease
agency questions
Organizations generate the filing documents
required to complete each CTD section, but
following initial approval, may need to modify
specific sections using a variation, amendment or
supplement. For example, additional clinical data
may be generated with the intent of expanding
the product’s use, and the sponsor will be required
to provide a new clinical study report (CSR) and
proposed label changes to support the new use.
Companies often initially generate an ICH-
style dossier first and use this to generate the
dossiers for non-ICH countries.
Regional Dossiers
The dossier’s content and structure may need to
be modified to meet each regulatory authority’s
requirements in the region or country in which
the organization wishes to register the product.
This may include a range of additional consider-
ations. Some examples are provided below, and
specific requirements are called out at a high
level in Table 15-2.
• Providing extra data—some regulatory
agencies require additional clinical
data representing the local population,
e.g., China, Japan, etc., or data with an
alternative comparator representing that
market’s standard of care.
• Additional declarations—legal letters of
authority, Certificates of Analysis, exe-
cuted batch manufacturing records all are
examples of country-specific additions.
• Local forms—application forms, local
language versions of clinical summa-
ries, Certificates of Pharmaceutical
Product (CPPs) confirming prior
approval in another jurisdiction (typi-
cally US or EU).