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Global Pharmaceutical and Biologics Regulatory Strategy, Second Edition
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monization among jurisdictions, partly because
each country’s clinical, social and financial
context can be so varied. However, several guid-
ing principles underpin many health technology
assessment (HTA) and reimbursement systems:
• Is the new medicine effective in the
population?
• Does it have advantages over currently
available therapies?
• Will it contribute to an overall health-
care savings (i.e., offset other costs)?
• Is it affordable?
The product value concept is incorporated in the
sponsor TPP, with contributions from health
outcomes, marketing and other integrated prod-
uct development team members.
Generally, a new product’s value and answers
to these questions are not forthcoming from a
clinical development program focused solely
on achieving regulatory approval. Regulatory
requirements compared with HTA authority
requirements are shown in Table 15-1.
On its own, the data package the regulatory
authority requires for marketing approval often
will be insufficient to meet HTA data require-
ments. In countries where reimbursement
is pivotal to a product’s market success, data
required to support reimbursement must be
incorporated into the product development plan
and regulatory strategy.
Late-stage clinical trial design consider-
ations impacting HTA assessments include:
• Active comparators—is a three-way
design incorporating a placebo and an
active comparator feasible? How will
the comparator be selected, as regional
standards of care may vary?
• Are quality of life and validated instru-
ments to evaluate patient preferences
planned?
• Does the trial use broader patient pop-
ulations?
Optimally, preapproval clinical trials will incor-
porate these data requirements. Increasingly,
postapproval studies are required. These may be
postapproval commitments as a condition of a
live licensing program or a risk management
program required by a regulatory agency. In
addition, postapproval observational studies and
registries provide evidence to support reim-
bursement submissions and continue to remove
uncertainty in the postmarket setting.
Global Product Development
CMC (Chemistry, Manufacturing and
Controls)
A CMC product development program focuses
on the drug substance and drug product’s formu-
lation, process development and presentation as
well as the manufacturing facility. From a global
Table 15-1. Comparison of Regulatory and HTA Requirements
Regulators HTA Authorities
Evaluate efficacy (therapeutic effect) Evaluate effectiveness, how well a treatment works in the practice of
medicine
Homogenous data Heterogeneous data
Risk/benefit Cost effectiveness
Comparator:
• placebo (FDA)
• active drug (EMA)
Comparator:
• current standard of practice
Focus is on the drug Focus is on population, cost and generalizing beyond data
Global Pharmaceutical and Biologics Regulatory Strategy, Second Edition
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
monization among jurisdictions, partly because
each country’s clinical, social and financial
context can be so varied. However, several guid-
ing principles underpin many health technology
assessment (HTA) and reimbursement systems:
• Is the new medicine effective in the
population?
• Does it have advantages over currently
available therapies?
• Will it contribute to an overall health-
care savings (i.e., offset other costs)?
• Is it affordable?
The product value concept is incorporated in the
sponsor TPP, with contributions from health
outcomes, marketing and other integrated prod-
uct development team members.
Generally, a new product’s value and answers
to these questions are not forthcoming from a
clinical development program focused solely
on achieving regulatory approval. Regulatory
requirements compared with HTA authority
requirements are shown in Table 15-1.
On its own, the data package the regulatory
authority requires for marketing approval often
will be insufficient to meet HTA data require-
ments. In countries where reimbursement
is pivotal to a product’s market success, data
required to support reimbursement must be
incorporated into the product development plan
and regulatory strategy.
Late-stage clinical trial design consider-
ations impacting HTA assessments include:
• Active comparators—is a three-way
design incorporating a placebo and an
active comparator feasible? How will
the comparator be selected, as regional
standards of care may vary?
• Are quality of life and validated instru-
ments to evaluate patient preferences
planned?
• Does the trial use broader patient pop-
ulations?
Optimally, preapproval clinical trials will incor-
porate these data requirements. Increasingly,
postapproval studies are required. These may be
postapproval commitments as a condition of a
live licensing program or a risk management
program required by a regulatory agency. In
addition, postapproval observational studies and
registries provide evidence to support reim-
bursement submissions and continue to remove
uncertainty in the postmarket setting.
Global Product Development
CMC (Chemistry, Manufacturing and
Controls)
A CMC product development program focuses
on the drug substance and drug product’s formu-
lation, process development and presentation as
well as the manufacturing facility. From a global
Table 15-1. Comparison of Regulatory and HTA Requirements
Regulators HTA Authorities
Evaluate efficacy (therapeutic effect) Evaluate effectiveness, how well a treatment works in the practice of
medicine
Homogenous data Heterogeneous data
Risk/benefit Cost effectiveness
Comparator:
• placebo (FDA)
• active drug (EMA)
Comparator:
• current standard of practice
Focus is on the drug Focus is on population, cost and generalizing beyond data