Page 63 - Biomedical Engineering and Design Handbook Volume 2, Applications

42 MEDICAL DEVICE DESIGN

FDA is required to respond within 30 days, if not, the sponsor may proceed. FDA may approve,
disapprove, or approve with conditions and modifications. This means that FDA may conditionally
approve the IDE so that the sponsor may proceed, although requiring that certain conditions be met.
Once IDE approval is received for a study, a sponsor may begin the difficult process. The spon-
sor must establish a protocol for the study. This is a daunting document which may run to over a hun-
dred pages. The protocol describes the methodology for the study and includes a detailed analysis of
why the study is scientifically sound. This is a pivotal document in the study. It must be followed by
the sponsor and all investigators.
The sponsor must enroll sites at which investigators will conduct the study under the protocol.
An IRB must approve the study for the site, including approving the wording of the informed con-
sent document. The sponsor must enter into contracts with the site and the investigator. The investi-
gator and study coordinator must be trained. A process must be put in place for recording all needed
data on forms provided by the sponsor.
During the study, the sponsor must monitor the investigation to ensure that it is compliant with
the regulations and the protocol. This usually involves periodic visits to the site. This is not to be con-
fused with auditing. Auditing a study is a retroactive activity which looks at data to determine if the
study was run properly. Monitoring is a continuing function during the study to ensure compliance.
Once a study is complete, the data are assembled and may be used for whatever the purpose of
the study was (FDA submission, reimbursement submission, publication, etc.).

2.14 QUALITY SYSTEM REGULATION

The Quality System Regulation (QSR) is a comprehensive control for the entire life cycle of a medical
device. The statutory basis is in what is known in the FDCA as good manufacturing practices (GMP).
The FDCA gives authority to FDA to regulate many products by prescribing GMP for their manufac-
ture. Different centers have implemented differing types of GMP, sometimes with differing names. For
example, GMP for pharmaceuticals are called cGMP, the small “c” meaning “current.” This was to indi-
cate that cGMPs are not a static standard. What is expected of a manufacturer changes over the years as
quality assurance practices improve and more is known about what to consider “best practices.”
When CDRH entirely revised GMPs for medical devices in 1997, it chose to use a new name indica-
tive of the new theory. The new language for device GMP was harmonized, to large extent, with the
then-current international standard for quality for devices: ISO 9001. Even though FDA regulations
were still based upon criminal law, unlike the EU standards-based theory, FDA chose to harmonize the
language of the regulation to achieve international consistency. The ISO standard was based upon a
pyramid of quality principles and controls known as a quality system. If one followed the quality sys-
tem, then quality product would logically flow. To indicate this harmonization, FDA named the new
system the QSR. Some within FDA tried to discourage the use of the acronym QSR, since it already
stood for a particular record within the system. However, these attempts have not quelled the instant
and complete adoption of the acronym QSR for the regulation.
The QSR had a scope much broader than the manufacturing controls of the old GMP. To harmo-
nize with ISO standards, FDA encompassed the entire design process into the QSR, so that it now
covers a product from cradle-to-grave.

(1) Who is covered?
Anyone who performs a manufacturing step, as defined by the QSR is covered. A manufacturer
is defined as

any person who designs, manufactures, fabricates, assembles, or processes a finished device.
Manufacturer includes but is not limited to those who perform the functions of contract sterilization,
installation, relabeling, remanufacturing, repacking, or specification development, and initial distributors
of foreign entities performing these functions.
Id. § 820.3(o).