International Combination Products
43
Introduction
Now that the jurisdiction of the combination
product has been established (see Chapter
4 Jurisdiction and Regulatory Pathway), the
sponsor or applicant can move to implement a
comprehensive regulatory strategy for the prod-
uct. Many cutting-edge combination products
are being introduced with innovative technol-
ogies (e.g., new technological delivery systems,
on-body wearable pump infusion systems,
mobile health technologies, and digital health
innovations). All combination products present
some developmental challenges, especially if
the sponsor or applicant is more accustomed to
developing and manufacturing only one of the
two or three constituent parts. Another com-
plexity of combination product development
is the fact that no single regulatory pathway
has been prescribed by the US Food and Drug
Administration (FDA).
As with other medical products, combina-
tion product development typically focuses on
the scientific and technical issues raised by the
particular product being developed. For a com-
bination product, these scientific/technical issues
will ordinarily reflect the combination product
itself as well as its constituent parts. When com-
bining products, such as drugs or biologics and
devices that are usually developed using different
regulatory pathways, certain critical developmen-
tal issues, including the interaction of the drug/
biologic and device constituents, may not be
readily apparent.
From the regulatory perspective of product
development, the regulatory professional should
begin by reviewing the data and information
accumulated for each constituent part of the
combination product to determine if any relevant
regulations, existing guidance documents, or
standards are available. These documents can be
used to gather information on the types of issues
that may be raised by the constituent parts of the
combination product. In consultation with sub-
ject matter experts (SMEs) in different functions
or departments in the company, the regulatory
professional can determine whether the guidance
can be followed as written or if any changes will
be needed to accommodate the specific con-
stituent parts. If the combination product has
constituent parts that share some of the same
regulatory requirements, such as a drug-biologic
combination product, adapting the guidance
document recommendations may be easier or
simpler to implement. However, for a combina-
tion product, such as a biologic-device, with each
constituent part having vastly different regulatory
requirements, it could be more difficult to adapt
the guidance recommendations. The bottom line
is that the regulatory professional needs to work
with the development team to implement an
approach that addresses the technical or scientific
issues without duplicative or redundant studies.
One other aspect that should not be forgotten
is to address issues that could occur because of
the type of combination product, e.g., issues
that could arise for a single-entity combination
product will differ vastly from the issues for a
5 Combination Product Development and
Meetings
43
Introduction
Now that the jurisdiction of the combination
product has been established (see Chapter
4 Jurisdiction and Regulatory Pathway), the
sponsor or applicant can move to implement a
comprehensive regulatory strategy for the prod-
uct. Many cutting-edge combination products
are being introduced with innovative technol-
ogies (e.g., new technological delivery systems,
on-body wearable pump infusion systems,
mobile health technologies, and digital health
innovations). All combination products present
some developmental challenges, especially if
the sponsor or applicant is more accustomed to
developing and manufacturing only one of the
two or three constituent parts. Another com-
plexity of combination product development
is the fact that no single regulatory pathway
has been prescribed by the US Food and Drug
Administration (FDA).
As with other medical products, combina-
tion product development typically focuses on
the scientific and technical issues raised by the
particular product being developed. For a com-
bination product, these scientific/technical issues
will ordinarily reflect the combination product
itself as well as its constituent parts. When com-
bining products, such as drugs or biologics and
devices that are usually developed using different
regulatory pathways, certain critical developmen-
tal issues, including the interaction of the drug/
biologic and device constituents, may not be
readily apparent.
From the regulatory perspective of product
development, the regulatory professional should
begin by reviewing the data and information
accumulated for each constituent part of the
combination product to determine if any relevant
regulations, existing guidance documents, or
standards are available. These documents can be
used to gather information on the types of issues
that may be raised by the constituent parts of the
combination product. In consultation with sub-
ject matter experts (SMEs) in different functions
or departments in the company, the regulatory
professional can determine whether the guidance
can be followed as written or if any changes will
be needed to accommodate the specific con-
stituent parts. If the combination product has
constituent parts that share some of the same
regulatory requirements, such as a drug-biologic
combination product, adapting the guidance
document recommendations may be easier or
simpler to implement. However, for a combina-
tion product, such as a biologic-device, with each
constituent part having vastly different regulatory
requirements, it could be more difficult to adapt
the guidance recommendations. The bottom line
is that the regulatory professional needs to work
with the development team to implement an
approach that addresses the technical or scientific
issues without duplicative or redundant studies.
One other aspect that should not be forgotten
is to address issues that could occur because of
the type of combination product, e.g., issues
that could arise for a single-entity combination
product will differ vastly from the issues for a
5 Combination Product Development and
Meetings