The FDA classifies medical products for regulatory purposes as drugs, devices, biologics, or combination products. The Center for Drug Evaluation and Research (CDER) is responsible for regulating drugs.17 A drug is defined as:
(A) articles recognized in the official United States Pharmacopoeia, official Homeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and (B) articles intended for use in the diagnostics, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure of any function of the body of man or other animals; and (D) articles for use as a component of any article specified in clause (A), (B), or (C)____18
In order to manufacture and market a new drug, a manufacturer must first file an Investigational New Device (IND) application to get approval for human subjects research.19 CDER must approve and monitor the clinical trials. Upon completion of clinical trials that test the product's safety, effectiveness, and dosage, CDER may approve a New Drug Application (NDA) if the benefits of the drug outweigh the risks.20 The manufacturer must comply with labeling requirements and a set of manufacturing regulations called the current Good Manufacturing Practices (GMPs).21 CDER can levy a "user fee" on manufacturers for reviewing a new drug application.22 The revenue generated from user fees must be used to make approval more efficient.
The Center for Devices and Radiological Health (CDRH) is responsible for regulating medical devices.23 A device is defined as:
an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is
1. recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them,
2. intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of diseases, in man or other animals, or
3. intended to affect the structure or any function of the body of man or other, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes.24
Devices are classified into three different categories: Class I, Class II, or Class III. Class I devices present the lowest risk and are subject to "general controls."25 Class II devices are subject to "special controls."26 Class III devices present the greatest risk and are subject to review for safety and effectiveness. In order to obtain FDA approval for clinical trials, a manufacturer must submit an Investigation Device Exception (IDE). In order to market the device, a manufacturer must submit a Premarket Approval Application (PMA), which imposes strict conditions on the manufacturing and labeling of the device. A new device that is "substantially equivalent" to a device already being marketed is not subject to review as a Class III device if the manufacturer obtains 510(k) approval.27 CDRH can also levy a "user fee" on manufacturers for reviewing a new device application.
While drugs and devices are regulated under the Food, Drug, and Cosmetic Act, biologics are regulated by Center for Biologics Evaluation and Research (CBER) primarily under the Public Health Service Act.28 A biologic is defined as:
a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound) applicable to the prevention, treatment, or cure of a disease or condition of human beings.29
CBER is responsible for regulating a wide variety of "biologics": blood and blood components, devices, allergenic extracts, vaccines, tissues, somatic cell and gene therapies, biotech derived therapeutics, and xenotransplanta-tion.30 CBER's responsibilities in regulating biologics are similar to CDER's responsibilities in regulating drugs. Approval must be granted for clinical testing of new biological products. In order to obtain a license to market, the agency must determine that a biological product is "safe, pure, potent, and manufactured accordingly."31
When a product is designated a "combination," the product's "primary mode of action" determines which center has primary jurisdiction over the product.32 A combination product is defined as:
1. A product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity;
2. Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products;
3. A drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect and where upon approval of the proposed product the labeling of the approved product would need to be changed, e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose; or
4. Any investigational drug, device, or biological product packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect.33
The Center chosen to regulate a combination product must apply the appropriate regulatory requirements to each part of the product. For example, if a product incorporates a biologic and a drug, and the primary mode of action is the biologic, CBER would regulate the product, in consultation with CDER, using applicable biologic and drug regulations.
A manufacturer can submit a request to have the product characterized as a drug, biologic, device, or combination product,34 and the intent of the manufacturer is often evaluated as evidence of how the product should be classified.35 Ultimately, the FDA is accorded substantial deference in making this determination.36
A manufacturer may prefer that the product be characterized in a particular way for two reasons. First, the FDAMA aimed to make the regulatory requirements for biologics and drugs similar,37 but there are significant differences between the approval process for devices and the approval process for drugs and biologics. There are statutory differences in approval times,38 and there may be a greater likelihood of securing approval for a product if it is designated as a device.39 Second, in the case of a combination product, a manufacturer may prefer that a particular Center have primary jurisdiction over the product for several reasons. A manufacturer may be more familiar with a particular Center or a manufacturer may want to target a particular Center for its tendency to evaluate certain types of evidence.40
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