Biomedical Engineering Reference
In-Depth Information
Combination products are typically the most difficult to regulate and take the longest to reach
the market. Biomaterial scaffolds alone without cells or growth factors are typically regulated
by the FDA as a device and are under CDRH jurisdiction.
The regulatory procedures are sufficiently complicated that typically a specialist in this
area is hired to manage this aspect of new product development. However, it is important
to have some idea of product regulation early on, since it, along with good research and
development, is needed to bring a medical product to clinical success. Toward that pur-
pose, the procedures utilized by the CDRH branch of the FDA will now be described.
The CDRH branch of the FDA utilizes classification of medical devices to assist with
determining the requirements for approval and the extent of regulatory control (http://
www.fda.gov/cdrh/devadvice/). Medical devices are placed into one of three classes.
Class I devices are those that have limited body contact and essentially pose no significant
risk. Class II devices require special controls and must usually meet some performance
standards to provide some assurance of safety. A device is placed in Class III if there is
insufficient information to determine that general or special controls are sufficient to pro-
vide reasonable assurance of its safety and effectiveness. A new device that is not substan-
tially equivalent to a device on the market will automatically be placed in Class III.
Examples of Class I medical devices include dental floss, a tongue depressor, a surgeon's
glove, and a clinical chemistry test system such as a pregnancy test. Examples of Class II
medical devices include a blood pressure cuff, an oxygen mask, dental impression material,
and an electrocardiograph. Examples of Class III medical devices include a heart valve, an
automated blood warming device, and a silicone inflatable or gel-filled breast prosthesis.
Classification is an important step of the FDA approval process, since it will determine
the extent of the testing required prior to use in humans and when the device can be sold.
At least 90 days prior to commercially distributing a new or substantially modified
device, a manufacturer must submit a premarket notification to the FDA. More than 99 per-
cent of the applications received by CDRH are cleared for marketing through the 510(k)
Premarket Notification process. The goal of this process is to demonstrate to the FDA that
the new device is substantially equivalent to an already approved predicate device. This
is accomplished through careful characterization by several complementary methods that
confirm the identity and purity of the substances involved, followed by completion of an
abbreviated form of the ASTM F748 and/or ISO 10993 test protocols and adherence to quality
system regulations. Quality system regulations include compiling a Device Master Record
and Design History File. Together these two files contain documentation of the procurement
process, the manufacturing details, all testing results—including assay verification tests—and
the details of the design rationale and design verification testing.
If a device does not qualify for 510(k) approval, then a full premarket application (PMA)
must be submitted containing all the required information on the safety and the effective-
ness of the device as determined through preclinical and clinical testing. There is a decision
tree in ISO 10993 that helps define which biocompatibility and safety testing is necessary
based on length of contact with the body and/or blood. Clinical trials are highly regulated
so human subjects are not exposed to significant risks without their knowledge. Carefully
documented and successfully completed in vitro and in vivo animal safety testing is
required at the time of application to begin a clinical trial. Human clinical trials typically
are divided into four phases: safety testing, efficacy testing, blinded efficacy compared to
