moves to Phase 3 it is essential to
make sure the specifications for
each component can be statistically
accommodated within the final overall system specification.
2. Device Design Controls — If the
device is part of a combination product filing, it will be reviewed with the
same rigor as a normal drug filing.
In the device world, this equates to
the same thoroughness as a pre-mar-ket approval (PMA) filing. However,
many devices are not developed with
a PMA in mind and do not have the
level of traceability between design,
testing, and verification within the
design history file to defend the final
device and system. Defining the regulatory strategy early in the development process is essential to avoiding
having to repeat or redo device and
system design activities as the product moves through the development
3. Product Release Strategy — If the
device has functionality as a stand-alone component of the system then
the QMS must be able to release the
drug, the device and the system independently. The principles behind drug release and
device release can often be discontinuous.
Reconciling a clear strategy early in the system development is essential to managing the
overall final specification establishment for
each component and the system.
Combination products are a complex technical
and regulatory undertaking for any organization.
Establishing a clearly defined and supported
PMOA is crucial to defining the regulatory strategy to be adopted. Ensuring the disparate QMS
components are addressed early within a system’s
development program will reduce the risk of
your program running into regulatory hurdles
that can cause your program to stumble or fail.
1. Global Market for Drug Device Combination
Products to be Driven by Growing Demand
for Minimally Invasive Surgical Procedures,
Transparency Market Research, http://www.
2. FDA Guidance for Industry, “Definition of
Primary Mode of Action of a Combination
Product,” August 2005.
3. FDA Guidance for Industry, “How to Write a
Request for Designation (RFD),” April 2011.
Bikash Chatterjee is President and Chief
Science Officer of Pharmatech Associates, a
Hayward, Calif.-based company that provides
consulting and services to the regulated life science
industry. Bikash has been involved in the biopharmaceutical, pharmaceutical, medical device, and
diagnostics industry for over 30 years. His expertise includes site selection, project management,
design, and validation of facilities for U.S. and
European regulatory requirements. bchatterjee@