January 28, 2019
Medical Product Regulation: Drugs, Biologics, and Devices
The Food and Drug Administration (FDA) regulates the
submission of an NDA, which may include restrictions on
safety and effectiveness of drugs, biologics, and devices
distribution or use of the drug.
(“medical products”) pursuant to its authorities under the
Federal Food, Drug and Cosmetic Act (FFDCA) and the
While prescription drugs are approved via an NDA under
Public Health Service Act (PHSA). Drugs and devices are
Section 505 of the FFDCA, biologics are licensed via a
approved or cleared under the FFDCA, whereas biologics
biologics license application (BLA) under Section 351 of
are licensed under the PHSA. Small molecule or chemical
the PHSA. The exception to this is certain natural source
drugs are chemically synthesized, while biologics are
biologics regulated as drugs under the FFDCA (e.g.,
derived from living organisms. All FDA-regulated medical
insulin). However, this will no longer be the case in March
products conceptually meet the definition of “drug.”
2020, when applications for biologics approved under the
Biologics are a subset of drugs, subject to many of the same
FFDCA will be deemed to be licenses under the PHSA. To
regulatory requirements. A device—an instrument,
obtain licensure, the sponsor must demonstrate in the BLA
apparatus, implement, machine, contrivance, implant, in
that the biologic and the facilities and processes for
vitro reagent, or other similar or related article—also meets
manufacturing the product are safe, pure, and potent. The
the definition of “drug”; however, unlike a drug or biologic,
requirements and review pathway for BLAs are generally
it “does not achieve its primary intended purposes through
similar to that for NDAs, and biologics are subject to
chemical action within or on the body ... and is not
certain FFDCA provisions (e.g., REMS).
dependent upon being metabolized for the achievement of
its primary intended purposes” (FFDCA Section 201(h)).
Medical Devices
FDA’s Center for Biologics Evaluation and Research
Medical devices are classified based on the risk posed to the
(CBER) oversees certain biologics (e.g., vaccines and gene
consumer. Class I devices are low-risk (e.g., elastic
therapies); the Center for Drug Evaluation and Research
bandages) and are generally exempt from premarket review.
(CDER) oversees chemical drugs and therapeutic biologics;
Class II and Class III devices are moderate-risk (e.g.,
and the Center for Devices and Radiological Health
powered wheelchairs) and high-risk (e.g., heart valves),
(CDRH) oversees medical devices and radiologic products.
respectively, and usually require premarket review. Unless
specifically excluded by regulation, all devices must meet
This In Focus broadly summarizes selected differences in
general controls, which include premarket and postmarket
statutory requirements among drugs, biologics, and devices.
requirements; for example, registration, labeling, and
It does not address every difference and is not meant to be a
compliance with CGMPs as set forth in FDA’s quality
comprehensive analysis of requirements.
system regulations (QSRs). As QSRs apply to many
different devices, the regulations are broad and flexible.
Premarket Requirements
Under most circumstances, drugs, devices, and biologics
In addition to general controls, Class II devices must meet
may be marketed only if they have been approved, cleared,
special controls, which are usually device-specific.
or licensed by FDA.
Premarket special controls include performance standards
and data requirements. Generally, Class II devices require
Prescription Drugs and Biologics
510(k) clearance demonstrating that a device is
To market a new prescription drug, the sponsor (generally
substantially equivalent to a device already on the market
the manufacturer) must submit a new drug application
(i.e., a predicate device). A 510(k) application typically
(NDA) demonstrating that the drug is safe and effective for
does not require submission of clinical data. Approximately
its proposed use. The law requires, among other things,
82% of total devices authorized for marketing in 2017 were
substantial evidence of effectiveness, and the agency has
cleared through the 510(k) clearance pathway. In November
some discretion to determine what evidence is necessary for
2018, FDA announced changes to modernize the 510(k)
NDA approval. During review, FDA officials evaluate the
clearance pathway, including sunsetting certain older
drug’s safety and effectiveness for the intended use (derived
predicate devices. However, the agency may need
from clinical trials); adequacy of manufacturing methods to
additional guidance from Congress before proceeding.
ensure the drug’s identity, strength, quality, and purity; and
accuracy of the proposed labeling. Sponsors must comply
Generally, Class III devices require a premarket approval
with current good manufacturing practice (CGMP)
application (PMA), with some exceptions. FDA issues an
regulations, which provide minimum requirements for the
approval order when a PMA demonstrates reasonable
methods, facilities, and controls used in manufacturing a
assurance that a device is safe and effective for its intended
drug. For drugs with certain safety risks, FDA may require
use(s). Effectiveness must be based on well-controlled
a risk evaluation and mitigation strategy (REMS) upon the
investigations, which generally means clinical trial data.
However, the law provides that other evidence, when
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Medical Product Regulation: Drugs, Biologics, and Devices
appropriate, may be used to establish effectiveness (e.g.,
work days of becoming aware of an event that requires
well-designed bench and/or animal testing) (see FFDCA
remedial action or a reportable event for which FDA made
§513(a)(3)(B) and “The Least Burdensome Provisions of
a written request. There are additional reporting
the FDA Modernization Act of 1997: Concept and
requirements for importers and user facilities (e.g.,
Principles; Final Guidance for FDA and Industry”).
hospitals). As with drugs and biologics, clinicians and
patients may report adverse events to the agency any time.
Regardless of risk, a new device with no substantially
equivalent predicate device is automatically designated
Postmarket special controls for Class II devices include
Class III unless the manufacturer submits a reclassification
surveillance and patient registries. For Class III devices,
request or petition. The de novo pathway allows for certain
FDA may impose additional postapproval controls in a
lower-risk, novel devices to be reclassified from a Class III
PMA approval order or by regulation subsequent to
designation to a Class I or II designation.
approval. These controls may overlap with special controls
for Class II devices but are generally more stringent and
Figure 1.Select Premarket Requirements
may include restriction of the sale, distribution or use of the
device, and annual postapproval reports, among others.
FDA can indirectly require a device labeling change by (1)
temporarily suspending a PMA approval order if, among
other things, the labeling is false or misleading (FFDCA
§515(e)), or (2) banning the device if it presents substantial
deception in the labeling, as specified (FFDCA §516(a)).
This is in contrast to the authority for drugs, which directly
allows FDA to require a labeling change without affecting
the drug’s approval status. FDA has mandatory recall
authority over medical devices (FFDCA §518(e)(1)).
Figure 2.Select Postmarket Requirements

Source: FFDCA, PHSA, and regulations at 21 C.F.R. Title 21.

Postmarket Requirements
Medical products are subject to various mandatory and
voluntary requirements once they are on the market.
Prescription Drugs and Biologics
Manufacturers must report all serious and unexpected
adverse events to FDA within 15 days of becoming aware

Source: FFDCA, PHSA, and regulations at 21 C.F.R. Title 21.
of them. Clinicians and patients may report adverse events

to the agency at any time. Once a drug is on the market,
Product Classification Challenges
FDA can require the manufacturer to conduct additional
studies or clinical trials based on newly acquired
Generally, a product that meets the statutory definition of a
information, and can require labeling changes based on
drug or biologic and is assigned to CDER or CBER will
information it gathers from mandatory and voluntary
have a higher standard of evidence, a potentially higher
adverse event reports (FFDCA §505(o)). FDA may require
requirement for supporting data, and a higher user fee than
a REMS after initial approval or licensing, if it becomes
a device assigned to CDRH. However, a product that is
aware of certain new information and determines the REMS
classified as a drug and assigned to CDER or CBER may be
is necessary to ensure that the drug’s benefits outweigh the
eligible for certain benefits that would not be available for a
risks. FDA conducts surveillance inspections once a drug is
product assigned to CDRH, such as data or market
on the market to assess compliance with manufacturing
protection in the form of regulatory exclusivity. At times,
standards, as well as for-cause inspections to investigate
there has been disagreement between FDA and product
concerns about product quality. The agency also monitors
sponsors regarding the jurisdictional determinations of
product integrity as the drug moves through the supply
certain drugs and devices and drug-device combination
chain. FDA has mandatory recall authority over biologics,
products. In addition, as new scientific evidence becomes
but generally not over drugs. However, FFDCA §569D, as
available, FDA may reconsider previous determinations.
added by the SUPPORT for Patients and Communities Act
For example, in December 2018, the agency announced its
(P.L. 115-271), provides for the recall of a controlled
intent to consider appropriate classification of certain
substance that would cause serious adverse health
hyaluronic acid (HA) intra-articular products that have been
consequences or death.
regulated as Class III devices and marketed under a PMA.
Recent scientific evidence suggests that HA achieves its
Medical Devices
primary intended purpose through chemical action within
Manufacturers must report device-related deaths, serious
the body, which may not meet the definition of a device.
injuries, and malfunctions within 30 days of becoming
aware of them and must submit a report to FDA within five
Agata Dabrowska, Analyst in Health Policy
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Medical Product Regulation: Drugs, Biologics, and Devices

IF11083
Victoria R. Green, Analyst in Health Policy


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https://crsreports.congress.gov | IF11083 · VERSION 2 · NEW

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