January 18, 2018
Medical Product Innovation and Regulation: Benefits vs. Risks
Prior to marketing in the United States, medical products
women and the injury of thousands associated with the use
are reviewed for safety and effectiveness by the Food and
of the Dalkon Shield, a contraceptive intrauterine device.
Drug Administration (FDA). Medical products regulated by
FDA include prescription drugs, medical devices, and
Efforts to Speed Product Access and FDA Review
biologics. During the premarket review process, FDA
Following the 1962 Kefauver-Harris Drug Amendments,
balances the benefits that patients may receive from using
early access (compassionate use) programs allowed some
the product against the harms or risks that some patients
patients to use drugs that were still under investigation;
may experience.
FDA published a rule regarding such access to cancer drugs
in 1979. In 1987, FDA formalized the steps to obtain an
Brief History of Medical Product Regulation
investigational drug outside a clinical trial (treatment IND,
Congressional action to regulate medical products has often
later codified by Congress). FDA established a policy in the
been in reaction to harm caused by an under regulated
early 1990s to allow access to HIV/AIDS drugs for patients
medical product. The Biologics Control Act of 1902 was
unable to enroll in a clinical trial (parallel track).
the first attempt to regulate a pharmaceutical product at the
national level. It was also the first premarket approval
FDA also created mechanisms to speed drug development
statute, in contrast to a retrospective postmarket product
and review. Priority review was begun by FDA in 1974 and
evaluation. The Biologics Control Act was passed in
modified by the agency in 1987 and 1992; it directs
response to deaths, many in children, from tetanus
attention and resources to drugs that offer a treatment
contamination of smallpox vaccine and diphtheria antitoxin.
advance. FDA launched fast track in 1988 to expedite the
The act focused on the manufacturing process and required
development, evaluation, and marketing of new therapies
that facilities be inspected before a federal license was
by allowing, for certain serious and life-threatening
issued to market a biological product.
conditions, FDA review to begin before clinical trials are
completed. FDA created the accelerated approval pathway
The regulation of drugs began with the 1906 Food and
in 1992 for serious or life-threatening diseases that lack
Drugs Act. The 1906 law did not involve any type of
effective treatment. It allows use of a surrogate endpoint,
premarket control over new drugs to ensure safety and did
via a biomarker test, to predict likely patient improvement
not include inspections or any other regulation of
from a new treatment, rather than a clinical endpoint
manufacturing facilities. The law focused on the drug label,
(symptom or death) that shows actual improvement in how
which could not be false or misleading, and required that
a patient feels or length of life. A January 2017 FDA report
the presence and amount of certain dangerous ingredients
states, however, that most biomarkers have not been shown
(such as alcohol, heroin, and cocaine) must be listed.
to reliably predict clinical outcomes due to the complexity
of diseases and therapies.
Responding to another safety incident, in 1938 Congress
replaced the Food and Drugs Act with the Federal Food,
Despite the use of these faster review mechanisms, industry
Drug, and Cosmetic Act (FFDCA). To make the taste of a
and patient groups continued to press Congress for a more
new sulfa drug more appealing to pediatric patients, a drug
rapid drug review process. The Prescription Drug User Fee
company added a solvent to its product, Elixir
Act of 1992 (PDUFA, P.L. 102-571) gave FDA authority to
Sulfanilamide. The solvent in the untested product was
collect fees from the pharmaceutical industry and to use the
highly toxic and caused the death of over 100 people,
revenue to support the drug review process by hiring
including many children. The FFDCA required that drug
additional personnel to evaluate NDAs. Medical device user
manufacturers submit, prior to marketing, a new drug
fees were added 10 years later by the Medical Device User
application (NDA) demonstrating, among other things, that
Fee and Modernization Act of 2002 (P.L. 107-250).
the product was safe. The FFDCA also included some
controls over manufacturing establishments.
Congress has addressed FDA user fee reauthorization in
five-year increments and often amends FDA regulatory
In 1962, Congress passed the Kefauver-Harris Drug
authorities at the same time. For example, Congress
Amendments to the FFDCA in reaction to the birth defects
codified priority review in PDUFA, fast track in the Food
and deaths associated with the use of thalidomide by
and Drug Administration Modernization Act of 1997 (P.L.
pregnant women in Europe. The 1962 law increased drug
105-115), and accelerated approval in the Food and Drug
safety provisions and required that manufacturers provide
Administration Safety and Innovation Act of 2012
evidence of drug effectiveness.
(FDASIA, P.L. 112-144). Congress itself created the
breakthrough drug category, another expedited review
The Medical Device Amendments of 1976 was the first
program added in FDASIA. However, studies have found
major legislation enacted to address the review of medical
that the term breakthrough drug is potentially misleading.
devices. The law was passed following the deaths of 17
The term is often misinterpreted by patients and physicians
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Medical Product Innovation and Regulation: Benefits vs. Risks
to mean that the “FDA designated breakthrough drug” is
reports from Government Accountability Office (GAO), the
more effective than other drugs when this has not been
Department of Health and Human Services (HHS)
proven. Use of this term in promotional material and
Inspector General (IG), the National Academies and others
advertising is of concern to some in academic medicine.
have criticized FDA monitoring systems and found
weaknesses in its oversight of postmarket drug safety.
In the 21st Century Cures Act (P.L. 114-255), Congress
crafted a new breakthrough device category to provide
A December 2015 GAO report states that “FDA has
priority review for devices that (1) provide more effective
supported efforts to shorten development and streamline the
diagnosis or treatment of a life-threatening or irreversibly
agency’s review of drug applications through expedited
debilitating condition and (2) represent breakthrough
pathways. However, we found problems with the agency’s
technologies for which no approved alternatives exist, offer
efforts to oversee and track potential safety issues and
significant advantages over existing alternatives, or are in
postmarket studies once those drugs are on the market.”
the best interest of patients. Proponents considered this
Moreover, it maintains that “FDA lacks comprehensive
necessary even though the time required for FDA premarket
plans to address the problems with its tracked safety issue
review of a device is less than drug review, and the standard
and postmarket study data.” FDA oversight of medical
of evidence for device review (reasonable assurance of
products has been on the GAO High-Risk List since 2009.
safety and effectiveness) is lower than drug review
The GAO list identifies agencies and program areas that are
(substantial evidence that the drug is safe and effective).
high risk due to certain vulnerabilities or are most in need
of transformation. FDA oversight of medical products also
Congressional reforms to FDA’s review process have
has been identified for over a decade by the HHS IG as one
primarily sought to speed market entry of medical products.
of the department’s top 10 management challenges.
These changes are often described as benefiting patients by
making innovative drugs or devices more rapidly available,
Regarding devices, FDA and others have identified a
while also being advantageous to the manufacturer.
number of limitations associated with the current medical
However, others say that the less fully regulators explore
device postmarket surveillance system. A February 2017
the safety and effectiveness of medical products before
GAO report on power morcellators illustrates the weakness
marketing, the higher the odds of unidentified adverse
of the current passive system: it relies on individuals
effects for patients. For example, patient harm and deaths
recognizing the harm caused by a device and sending an
might have been minimized if human trials had been
adverse event report to FDA. Although the agency is
required prior to widespread use of implanted devices such
expanding system capabilities, its new medical device
as the DePuy metal-on-metal hip and the Medtronic Sprint
postmarket monitoring system, the National Evaluation
Fidelis and St Jude Medical Riata cardiac leads (wires).
System for health Technology (NEST), is expected to be
under development for the next several years.
Examples of harm exist for drugs as well. A May 2017
JAMA study examined 222 novel therapeutics (183 drugs
Concluding Observations
and 39 biologics) approved by FDA from 2001 through
Medical products are not completely safe, nor are they
2010 and found that 71, or 32%, were affected by
equally effective for all individuals. Larger and longer
postmarket safety events. As a result, three products were
clinical trials would better detect rare or latent adverse
withdrawn from the market (new safety information
events, but some believe the wait is unreasonably long and
profoundly changed the risk/benefit balance), there were 61
that any risks are offset by earlier access to the benefits of
boxed warnings (for major, often life-threatening safety
innovative new treatments. However, innovative products
risks), and 59 safety communications (for non-life-
do not always result in therapeutic advances. In the rush to
threatening safety risks). Postmarket safety events were
market, it is important not to conflate medical product
more frequent among biologics, therapeutics for the
“innovation” with an actual therapeutic advance for
treatment of psychiatric disease, and therapeutics that
patients. An innovative mode of action in a drug or device
received accelerated approval. The study did not assess fast
may not necessarily improve the life of a patient. New is
track or breakthrough therapies.
not always better. A January 2017 FDA report found that
early studies can inaccurately predict safety and/or
A December 2017 JAMA report analyzed all 174 new drugs
effectiveness for medical products in a wide range of
and biologics approved by FDA from 2012 through 2016
diseases and patient populations. Shortening or otherwise
and found that 105, or 60%, used one or more expedited
diminishing the evidence-gathering phase on a new medical
programs. It assessed the median development time which
product may have harmful consequences for patients.
ranged from 8.0 years for products without an expedited
CRS Products
program to 4.8 years for those with breakthrough status.
CRS Report R41983, How FDA Approves Drugs and
Regulates Their Safety and Effectiveness
FDA has systems to monitor drug safety following
approval. Drug manufacturers are required to report adverse
CRS Report R42130, FDA Regulation of Medical Devices
events to FDA, and drugs with potential safety issues may
be tracked via an internal database. FDA also may require a
CRS Report R44620, Biologics and Biosimilars:
drug sponsor to conduct postmarket safety and
Background and Key Issues
effectiveness studies. Confirmatory trials are especially
Judith A. Johnson, Specialist in Biomedical Policy
important when accelerated approval is used because the
safety picture is less fully developed. However, numerous
IF10813
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Medical Product Innovation and Regulation: Benefits vs. Risks


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