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Chapter 15: Global Regulatory Strategy
responsibility, in consultation with the global
multidisciplinary development team. Some
markets do not accept applications until one of
the ICH (i.e., reference) countries completes
its review. Once this initial review is complete,
a CPP can be issued confirming a satisfactory
review was completed in another jurisdiction.
This can mean other markets can do a slightly
abbreviated review based on the fact the prior
review has occurred, known as a reliance mech-
anism. This allows regulatory submission to take
place in waves.
Key considerations when planning a filing
timeline include:
• availability of required filing data, e.g.,
local market data
• prior reviews, e.g., in an ICH country
(US, EU, Japan) (including an ability
to leverage responses to these questions
elsewhere)
• launch time commercial driver
(impacted by market dynamics), e.g.,
when does the organization want to
initiate distribution, as soon as possible
or at a defined time
• resource availability to complete the
filing (including responding to agency
questions)
• desired filing sequence (knowing agen-
cies discuss reviews with each other, and
agreement on specific label language
in one region can impact the review
outcome in another)
Lifecycle Management
Postapproval Commitments
At the time of initial registration, a company
will have limited experience and exposure with
its drug and some uncertainty. In the past,
regulatory approval was ‘all or nothing.’ When a
product is approved for marketing, a regulatory
agency has relied almost exclusively on sponta-
neous adverse reporting programs to monitor a
new product’s safety in the marketplace.
More recently, an increasing number of
jurisdictions require Risk Management Plans
(RMPs) to be submitted as part of marketing
applications and require formal postapproval
activities to ensure appropriate prescribing and
usage and to monitor and manage product safety.
Although detailed RMP guidelines and formats
vary across jurisdictions, the risk management
principles articulated in the International Stan-
dard ISO 31000 generally apply.3
From early planning and as product devel-
opment progresses, ISO 31000’s principles can be
applied to enable early product risk identification
and assessment, together with mitigation plans to
minimize these risks during further development,
at product launch and postapproval.
When planning and preparing marketing
applications for each jurisdiction, the residual
risks and management strategies identified in
a global RMP can be customized to produce
jurisdiction-specific RMPs.
During the evaluation process, the regula-
tory agency may identify new risks or request
alternate management strategies. These may be
country-specific issues, such as those associated
with prescribing patterns or healthcare practices.
In these instances, country-specific responses are
required. Alternatively, these may potentially be
issues relevant around the globe. Coordinating
global risk management planning and incorpo-
rating these issues into RMPs and postapproval
activities provide the opportunity to maintain
a globally harmonized lifecycle maintenance
approach. Issues initially restricted to one country
or jurisdiction may, in time, be applicable to other
countries, and the understanding and knowledge
gained then can be shared for mutual benefit.
The need to globally coordinate postapproval
commitments will increase as adaptive licenses
are granted. Adaptive licenses acknowledge data
continue to accumulate after a license is granted,
and access is best addressed by repeat cycles of
learning and confirming (re-licensing) over the
product lifecycle continuum.
Increased monitoring of real-world perfor-
mance (Real World Evidence, RWE), including
postauthorization efficacy and safety studies
Chapter 15: Global Regulatory Strategy
responsibility, in consultation with the global
multidisciplinary development team. Some
markets do not accept applications until one of
the ICH (i.e., reference) countries completes
its review. Once this initial review is complete,
a CPP can be issued confirming a satisfactory
review was completed in another jurisdiction.
This can mean other markets can do a slightly
abbreviated review based on the fact the prior
review has occurred, known as a reliance mech-
anism. This allows regulatory submission to take
place in waves.
Key considerations when planning a filing
timeline include:
• availability of required filing data, e.g.,
local market data
• prior reviews, e.g., in an ICH country
(US, EU, Japan) (including an ability
to leverage responses to these questions
elsewhere)
• launch time commercial driver
(impacted by market dynamics), e.g.,
when does the organization want to
initiate distribution, as soon as possible
or at a defined time
• resource availability to complete the
filing (including responding to agency
questions)
• desired filing sequence (knowing agen-
cies discuss reviews with each other, and
agreement on specific label language
in one region can impact the review
outcome in another)
Lifecycle Management
Postapproval Commitments
At the time of initial registration, a company
will have limited experience and exposure with
its drug and some uncertainty. In the past,
regulatory approval was ‘all or nothing.’ When a
product is approved for marketing, a regulatory
agency has relied almost exclusively on sponta-
neous adverse reporting programs to monitor a
new product’s safety in the marketplace.
More recently, an increasing number of
jurisdictions require Risk Management Plans
(RMPs) to be submitted as part of marketing
applications and require formal postapproval
activities to ensure appropriate prescribing and
usage and to monitor and manage product safety.
Although detailed RMP guidelines and formats
vary across jurisdictions, the risk management
principles articulated in the International Stan-
dard ISO 31000 generally apply.3
From early planning and as product devel-
opment progresses, ISO 31000’s principles can be
applied to enable early product risk identification
and assessment, together with mitigation plans to
minimize these risks during further development,
at product launch and postapproval.
When planning and preparing marketing
applications for each jurisdiction, the residual
risks and management strategies identified in
a global RMP can be customized to produce
jurisdiction-specific RMPs.
During the evaluation process, the regula-
tory agency may identify new risks or request
alternate management strategies. These may be
country-specific issues, such as those associated
with prescribing patterns or healthcare practices.
In these instances, country-specific responses are
required. Alternatively, these may potentially be
issues relevant around the globe. Coordinating
global risk management planning and incorpo-
rating these issues into RMPs and postapproval
activities provide the opportunity to maintain
a globally harmonized lifecycle maintenance
approach. Issues initially restricted to one country
or jurisdiction may, in time, be applicable to other
countries, and the understanding and knowledge
gained then can be shared for mutual benefit.
The need to globally coordinate postapproval
commitments will increase as adaptive licenses
are granted. Adaptive licenses acknowledge data
continue to accumulate after a license is granted,
and access is best addressed by repeat cycles of
learning and confirming (re-licensing) over the
product lifecycle continuum.
Increased monitoring of real-world perfor-
mance (Real World Evidence, RWE), including
postauthorization efficacy and safety studies