Medical Product Regulation: Drugs, Biologics, and Devices

Medical Product Regulation: Drugs, Biologics, and Devices

Updated May 26, 2023
Medical Product Regulation: Drugs, Biologics, and Devices
The Food and Drug Administration (FDA) regulates the
While drugs are approved via an NDA under Section 505 of
safety and effectiveness of drugs, biologics, and devices
the FFDCA, biologics are licensed via a biologics license
(“medical products”) pursuant to its authorities under the
application (BLA) under Section 351 of the PHSA. To
Federal Food, Drug and Cosmetic Act (FFDCA) and the
obtain licensure, the sponsor must demonstrate in the BLA
Public Health Service Act (PHSA). Drugs and devices are
that the facilities and processes for biologics manufacturing
approved or cleared under the FFDCA, whereas biologics
meet standards ensuring the product is safe, pure, and
are licensed under the PHSA. Small molecule or chemical
potent (i.e., effective). The requirements and review
drugs are chemically synthesized, while biologics are
pathway for BLAs are generally similar to those for NDAs,
derived from living organisms. All FDA-regulated medical
and biologics are subject to certain FFDCA provisions.
products conceptually meet the definition of “drug.”
Biologics are a subset of drugs, subject to many of the same
For prescription drugs and biologics with certain safety
regulatory requirements. A device—“an instrument,
risks, FDA may require a risk evaluation and mitigation
apparatus, implement, machine, contrivance, implant, in
strategy (REMS) upon the submission of an NDA, which
vitro reagent, or other similar or related article”—also
may include restrictions on distribution or use of the drug or
meets the definition of “drug”; however, unlike a drug or
biologic.
biologic, it “does not achieve its primary intended purposes
through chemical action within or on the body ... and is not
Medical Devices
dependent upon being metabolized for the achievement of
Medical devices are regulated based on the risk posed to the
its primary intended purposes” (FFDCA §201(h)). FDA’s
consumer: Class I devices are low-risk, Class II devices are
Center for Biologics Evaluation and Research (CBER)
moderate-risk, and Class III devices are high-risk. Unless
oversees certain biologics (e.g., vaccines and gene
specifically excluded by regulation, all devices must meet
therapies); the Center for Drug Evaluation and Research
general controls, which include both premarket and
(CDER) oversees chemical drugs and other biologics (e.g.,
postmarket requirements. General controls include, for
certain monoclonal antibodies and immunomodulators);
example, 510(k) premarket notification, registration, listing,
and the Center for Devices and Radiological Health
and compliance with CGMPs as set forth in FDA’s quality
(CDRH) oversees medical devices and radiologic products.
system regulation (QSR). Class II devices must meet, in
addition to general controls, special controls, which are
This In Focus broadly summarizes selected differences in
usually device-specific. Premarket special controls include
statutory requirements among drugs, biologics, and devices.
performance standards and premarket data requirements.
It does not address every difference and is not meant to be a
Almost all Class I devices are exempt from the 510(k)
comprehensive analysis of requirements.
premarket notification requirement, whereas almost all
Class II devices require 510(k) clearance prior to
Premarket Requirements
marketing. A 510(k) submission must demonstrate that a
Under most circumstances, drugs, devices, and biologics
device is substantially equivalent to a legally marketed
may be marketed only if they have been approved, cleared,
predicate device, which typically does not require
or licensed by FDA.
submission of clinical data, although it may in certain cases.
In November 2018, FDA announced proposed changes to
Prescription Drugs and Biologics
modernize the 510(k) clearance pathway, including the
To market a new drug, the sponsor (generally the
preferential use of modern predicate devices and
manufacturer) must submit to FDA for review a new drug
development of updated pathways.
application (NDA) demonstrating that the drug is safe and
effective for its proposed use. FDA has some discretion
Class III devices are subject to premarket approval
when determining what evidence is necessary for NDA
application (PMA) requirements, with some exceptions, in
approval. During review, FDA officials evaluate the drug’s
addition to general controls. FDA issues an approval order
safety and effectiveness (derived from clinical trials) for its
when a PMA demonstrates reasonable assurance that a
intended use; adequacy of manufacturing methods to ensure
device is safe and effective for its intended use(s). Safety
the drug’s identity, strength, quality, and purity; and
and effectiveness must be based on valid scientific
accuracy of the proposed labeling. Sponsors for both drug
evidence, which is generally derived from well-controlled
and biologic products must comply with current good
investigations, usually clinical trials. However, the law
manufacturing practice (CGMP) regulations, which provide
provides that other evidence, when appropriate, may be
minimum requirements for the methods, facilities, and
used to establish effectiveness (e.g., well-designed bench
controls used in manufacturing.
and/or animal testing) (FFDCA §513(a)(3)(B) and “The
Least Burdensome Provisions: Concept and Principles”).
Regardless of risk, a new device with no substantially
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Medical Product Regulation: Drugs, Biologics, and Devices
equivalent predicate device is automatically designated
controls for Class II devices include postmarket
Class III unless the manufacturer submits a reclassification
surveillance (e.g., mandated studies) and patient registries.
request or petition. The de novo pathway allows for certain
For Class III devices, FDA may impose additional
lower-risk, novel devices to be reclassified from Class III to
postapproval controls in a PMA approval order or by
Class I or II; devices reviewed through this pathway
regulation subsequent to approval. These controls may
successfully are authorized for marketing, create a new
overlap with special controls for Class II devices but are
device type, and may serve as a predicate going forward.
generally more stringent and may include postapproval
studies; restriction of the sale, distribution or use of the
Figure 1. Select Premarket Requirements
device; and postapproval reports. FDA can indirectly
require a device labeling change by (1) temporarily
suspending a PMA approval order if, among other reasons,
the labeling is false or misleading (FFDCA §515(e)), or (2)
banning a device if it presents substantial deception in the
labeling (FFDCA §516(a)). FDA has mandatory recall
authority over medical devices (FFDCA §518(e)), although
this authority is rarely used.
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.

Source: FFDCA, PHSA, and regulations at 21 C.F.R. Title 21.
Prescription Drugs and Biologics
Product Classification Challenges
Manufacturers must report all serious and unexpected
adverse events to FDA within 15 days of becoming aware
Generally, a product that meets the statutory definition of a
of them. Clinicians and patients may report adverse events
drug or biologic and is assigned to CDER or CBER will
to the agency at any time. Once a drug is on the market,
necessitate a higher standard of evidence, user fee, and
FDA can require the manufacturer to conduct additional
requirement for supporting data than will a device assigned
studies or clinical trials based on newly acquired
to CDRH. However, a product that is classified as a drug
information, and can require labeling changes based on
and assigned to CDER or CBER may be eligible for certain
information it gathers from mandatory and voluntary
benefits that would not be available for a product assigned
adverse event reports (FFDCA §505(o)). FDA may require
to CDRH, such as data or market protection in the form of
a REMS after initial approval or licensing if it becomes
regulatory exclusivity. At times, there has been
aware of certain new information and determines the REMS
disagreement between FDA and product sponsors regarding
is necessary to ensure that the drug’s benefits outweigh the
the jurisdictional determinations for certain drugs and
risks. FDA conducts various types of inspections, including
devices and drug-device combination products. For
surveillance inspections once a drug is on the market to
example, in 2019, Genus Medical Technologies sued FDA
assess compliance with manufacturing standards, as well as
for its decision to classify barium sulfate contrast imaging
for-cause inspections to investigate concerns about product
agents as drugs rather than devices. This was ultimately
quality. FDA also monitors product integrity as a drug
settled legislatively, as Section 3621 of the Consolidated
moves through the supply chain. FDA has mandatory recall
Appropriations Act, 2023 (P.L. 117-328), deemed any
authority over biologics, but generally not drugs. However,
contrast agent, among other substances, to be a drug under
FFDCA Section 569D, added by P.L. 115-271, provides for
the FFDCA. Additionally, as new scientific evidence
the recall of a controlled substance that would cause serious
becomes available, FDA may reconsider previous
adverse health consequences or death.
determinations. For example, in December 2018, the
agency announced its intent to reconsider classification of
Medical Devices
certain hyaluronic acid (HA) intra-articular products that
Manufacturers must report device-related deaths, serious
have been regulated as Class III devices (83 Federal
injuries, and malfunctions within 30 days of becoming
Register 64844). New evidence suggests that HA achieves
aware of them and must submit a report to FDA within five
its primary intended purpose through chemical action
work days of becoming aware of (1) an event that requires
within the body, which may not meet the definition of a
remedial action, or (2) a reportable event for which FDA
device.
made a written request. There are additional reporting
requirements for importers and user facilities (e.g.,
Amanda K. Sarata, Specialist in Health Policy
hospitals). Clinicians and patients may report adverse
Hassan Z. Sheikh, Analyst in Health Policy
events to the agency at any time. Postmarket special
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Medical Product Regulation: Drugs, Biologics, and Devices

IF11083

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https://crsreports.congress.gov | IF11083 · VERSION 5 · UPDATED