Biomedical Engineering Reference
In-Depth Information
are produced by cells and can potentially be regulated by CBER. It is important to note, though,
that the primary mode of the effects of biologics is metabolic. Thus, ACI, a procedure that requires
manipulation of the autologous cells that will metabolize and produce tissue
in situ
, is regulated by
CBER.
A Biologics License Application (BLA) must be filed for the permission to introduce a bi-
ologic product into the market, and the BLA is regulated under 21 CFR 600 to 680. Applicants
for a license must comply with requirements set forth by Form 356h, which includes the applicant
information, product and manufacturing information, pre-clinical studies, clinical studies, and la-
beling. Of substantial burden are clinical studies, which can be slow and costly. For implants, the
FDA has had a history of classifying most orthopaedic implants as medical devices, which have
their own regulatory Center. In the case of ACI, the resulting implant is expected to generate tissue
through metabolic means and, as a cell slurry, cannot withstand loading as an implant would and,
thus, probably cannot be classified as a device. Applying for approval as a device, e.g., through the
510(k), may be less burdensome as explained in the next section.
Firms that manufacture, repackage, relabel, and/or import medical devices sold in the United
States are subject to regulation by the Center for Devices and Radiological Health (CDRH). (As
an aside, CDRH also regulates radiation-emitting electronic products, including x-ray systems, ul-
trasound equipment, microwave ovens and color televisions.) A medical device is “an instrument,
apparatus, implement, machine, contrivance, implant,
in vitro
reagent, or other similar or related
article, including any component, part, or accessory, which is intended for use in the diagnosis of
disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease” [
834
].
Tissue engineered cartilage, as an implant, may be regulated by CDRH even if it contains biologics or
drugs, depending on the assignment by the Office of Combination Products. The primary mode of
effect for devices is mechanical or electrical. Implants whose primary function is to bear mechanical
load (as tissue engineered cartilage is designed to function) may have CDRH as its primary regu-
lator. Devices regulated within the CDRH fall into three classes and have different requirements
that the manufacturer must fulfill prior to introducing a product to market. As CDRH has been
assigned jurisdiction over most orthopaedic implants, pathways to market through this Center will
be described in the next section.
A medical product intended to promote public health must be both safe and effective. Scientific
studies conducted to demonstrate both of these criteria can cost both time and money. The FDA,
charged with reviewing the scientific data, must also devote similar resources. A shorter time-to-
market can potentially result in the earlier realization in benefits to public health or in lack of
adequate data to ensure safety. While excessive burdens in testing can deplete a company's resources
and stifle product innovation, small clinical studies might not be able to detect rare adverse events
associated with a device.Through its Centers and Offices, the FDA performs a balancing act between
expediency and assurance of public welfare. To ease the regulatory burden of industry, FDA has
established intercenter agreements, e.g., between the CBER and the CDRH, and between the
CDER and the CDRH. Also, in order to ensure that adequate effort is expended in evaluating a
