Mr. Chairman, Members of the Committee, I am Jane E.
Henney, Commissioner of Food and Drugs at the Food and Drug Administration (FDA or the
Agency). I am very pleased to have the opportunity to be here today, nearly one year after
my confirmation as Commissioner, to discuss the Agencys progress on its
implementation of the Food and Drug Administration Modernization Act of 1997 (FDAMA or
Modernization Act). I have made a strong commitment and given high priority to
implementing the Modernization Act in a manner consistent with the letter and spirit of
Over the past two years, FDA has worked diligently on implementation of this new
statute, which touches nearly every facet of the Agencys mission, and we have met
nearly every statutory deadline along the way. We have issued dozens of regulations,
guidance documents, Federal Register notices, and reports in order to carry out the
goals of this wide-reaching law. As I will discuss, however, the success of the
Modernization Act can be measured in more profound ways. With the tools provided by FDAMA,
FDA is becoming a stronger, better Agency, one whose actions remain firmly based in
science to promote and protect the public health.
The value of a strong, science-based regulatory agency cannot be overstatedit
reaps public health benefits for both individual citizens and the nation as a whole. A
regulatory agency that sets and meets high scientific standards provides a high level of
assurance to our citizens; (1) assurance that product risks are minimized; (2)
assurance that consumers receive reliable information to assess and manage the remaining
risks in concert with a health professional, or on their own; and (3) assurance that
reviews for new products are conducted in a predictable and timely manner that gives
patients early access to new safe and effective products.
A regulatory agency using review procedures that are open and transparent provides
consumers with confidence in the decisions made about the products that they take and give
to their families, and provides industry with the confidence that the Agencys
decisions are fair and based in science. Consumer confidence in FDA also benefits the
industry by increasing assurance of the quality of the products they make available to
From an economic standpoint, a strong, high-performance regulatory agency stimulates
innovation, enhances U.S. competitiveness in global markets, provides a level playing
field for industry, and strengthens the domestic economy as a whole by inviting increased
foreign investment and contributing to reduced health care costs.
I would like to focus today on how FDAs implementation of the Modernization Act
is helping to produce the following outcomes: (1) enhancing the public health; (2)
making our regulatory processes more effective and efficient; and (3) increasing consumer
and industry confidence through open, transparent processes and collaboration.
Public Health Benefits
The Modernization Acts benefits to the public health can be grouped in two
categories: greater patient access to new medical products and more effective management
of FDAs limited resources. There are a number of FDAMA provisions that help ensure
greater patient access to medical products. The first of these provisions involves the
reauthorization of the Prescription Drug User Fee Act (PDUFA) in section 101. User fees
provide the Agency with needed resources to review applications in a timely manner. The
result is expedited access to a greater number of important new drugs.
As a measure of the success of this program, FDA exceeded all of its PDUFA performance
goals in 1998. I am extremely proud of the Agencys exceptional performance in this
area. Because of this review performance, our median time to approval for priority new
drugs was just six months, and for all new drug applications it was one year. For
biologics, the median approval time for PDUFA product license applications and biologics
license applications has declined dramatically from 31.3 months in FY 1993 to less than 12
months just five years later. FDAs review of non-PDUFA license applications has also
improved, although not as dramatically as the PDUFA license applications.
Over the past five years, pharmaceutical firms have introduced 172 new molecular
entities into the marketa sizable increase over prior decades. Since the enactment
of PDUFA (1992), the average number of new products approved per year has increased by 40
percent, and in 1998, 75 percent of world-wide molecular entities were first launched in
the United States
Drugs are now being reviewed in the United States
as fast or faster than anywhere in
the world, without compromising the very stringent standards that Americans have come to
expect. Although European pharmaceutical companies dominated the industry ten years ago,
U.S. companies now have an overwhelming lead in world markets. This translates into job
creation in the U.S., as well as increased foreign investment in U.S. companies.
Let me take a moment to mention the products themselves. Product approvals in 1998
included a high number of products that represent significant advances over the products
that were previously available. Important new therapies brought to market in the past year
include: several new treatments for breast and bladder cancer, influenza, new arthritis
drugs, new AIDS therapies for both adults and children.
In the biotech area, 1998 saw the approval of products that reduce the need for
frequent platelet transfusions after chemotherapy, prevent acute kidney transplant
rejection, and treat deep diabetic foot and leg ulcers. These are only a few exciting
examples of products that are being made available without delay to the patients who need
Another FDAMA success story is the fast track provision in section 112. In the fast
track provision, Congress codified FDAs accelerated approval regulations and thus
codified our approach to expedited drug development. Fast track is meant to facilitate the
development, and expedite the review, of drugs that are intended to treat a serious or
life-threatening condition and that demonstrate the potential to address a serious unmet
Under the new law, our effectiveness standard is unchanged. There must be substantial evidence that the drug will have the beneficial effect it purports to have. The new provision also recognizes, however, that clinical research techniques have changed and progressed and that
substantial evidence of effectiveness can come from sources we have not traditionally
relied on. To best meet public health needs, we are taking into account a full array of
appropriate evidenceincluding evidence from studies with surrogate endpoints. This
allows us to make our risk/benefit determination both accurately and more rapidly than
Since the passage of the Modernization Act, we have granted fast track designation for
a wide range of therapiesnot just for AIDS and cancer drugs, as some believe, but
for drugs to treat atherosclerotic vascular disease, acute stroke, diabetes, adult
respiratory distress syndrome and pancreatitis. As of September 15, 1999, FDAs
Center for Drug Evaluation and Research (CDER) had received 59 requests for fast track
designation41 were granted, 14 denied, and 4 are still pending. FDAs Center
for Biologics Evaluation and Research (CBER) had received 34 requests20 were
granted, 10 denied, and 4 are still pending.
The approvals that have occurred under the fast track program demonstrate the
Agencys successful implementation of expedited review. Since we began implementing
this provision, we have approved four productsHerceptin, a monoclonal antibody, for
metastic breast cancer (in 4.7 months), Enbrel for rheumatoid arthritis (in 5.8 months),
and Ziagen and Agenerase for the treatment of HIV (in less than 5 months and 6 months,
respectively). With Herceptin and Enbrel, the Agency employed a "rolling
review"which is another important part of the fast track provision. As
implemented by FDA, this program is plainly helping to ensure that important therapies for
serious and life-threatening illnesses are being brought as quickly as possible to the
patients who need them.
To provide clear information to industry regarding participation in the fast track
process, we issued a guidance document on this provision last fall. This document defines
the criteria for qualification for the fast track drug product development program, sets
out the process for designation as a fast track drug product, and describes programs for
expediting development and review of fast track products. The Agency has received feedback
that commended this document as an excellent resource for sponsors who are interested in
receiving fast track designation for their products.
FDAMAs pediatric exclusivity provision in section 111 is also helping to assure
access to new therapies, in this case, by children whose access has historically been
limited by inadequate information about the safe and effective use of drugs in the
pediatric population. Ensuring that there is adequate pediatric use information for drugs
and biologics has long been a high priority for the Agency. The pediatric exclusivity
provision of FDAMA has provided a successful complement to the Agencys final
rulemaking requiring pediatric testing for drugs issued in November 1998. We are pleased
to report that there has been an enthusiastic response from industry to the incentives
offered by this provision. As you know, in June 1998, we issued written guidance to
communicate to industry our plans for implementation of the pediatric program, and updated
this document in October 1999 to provide additional information to industry.
The numbers speak for themselves. Between June 1998, when the guidance document was
published, and September 1999, FDA has received over 150 proposed pediatric study
requests. We have taken action on 143.
FDA believes that this program holds the promise of significantly expanding
childrens access to important therapeutics and is committed to its successful
implementation. Since June 1998, we have reduced our average time in issuing a written
request from about 200 days to an average of 60 days. As of September 1, 1999, there were
37 pending proposals, of which only 7 had been with us for more than 120 days. The
majority of delayed responses resulted from our desire to resolve serious regulatory,
medical, scientific, or ethical questions raised by the prospect of study of these
products or classes of products in children. We actively engage in resolving these issues,
often in collaboration with the sponsor. FDA now takes a maximum of 120 days to take
action on a study request, except in extraordinary circumstances. Through our continued
work through mechanisms such as our Pediatric Advisory Subcommittee, we will continue to
move toward our goal of having adequate pediatric use labeling information for all drugs
used in children.
Just as it is important to get the most complete information about all patient
populations on a drugs label, it is also important to get all of the information
about a drugs uses on the label. This is why Congress directed FDA to take steps to
encourage the submission of supplemental applications for new uses for approved medical
products, and steps to ensure that such applications are acted upon expeditiously. Since
enactment, the Agency has made programmatic changes in each Center to encourage
supplemental applications for new uses, and ensure that the Agency acts on the
applications that it receives in a timely manner. The Agency has also issued guidance that
clarifies what is needed to demonstrate effectiveness for a new use.
In an ideal world, all medical products would be the subjects of a thorough study of
safety and effectiveness before they are given to patients. In the real world, however,
Congress and FDA realized that there are times when a patients interest is best
served by getting the product as quickly as feasible, sometimes before a complete
evaluation and review can be finished. The expanded access provision (section 402) of the
Modernization Act was included in the legislation in order to facilitate access by
patients with serious and life-threatening illnesses to promising, yet unapproved new
products. By codifying the Agencys current procedures for this program, the statute
ensures that this program will continue to provide expanded access to patients in the
Congress also recognized that there are limited circumstances when there are too few
subjects to justify a full-scale evaluation of a medical device. The humanitarian use
device provision (section 203) provides an easier path to market for devices used to treat
rare conditions or diseases. Under this provision, a manufacturer is not required to meet
the effectiveness requirements in the statute, but rather must show that the device does
not pose an unreasonable or significant risk of illness or injury, and that the probable
benefit to health outweighs the risk from its use. Since implementation of the
Modernization Act, our Center for Devices and Radiological Health (CDRH) has approved 12
humanitarian use devices, including: a fetal bladder stent, to treat urinary tract
obstruction in unborn babies; an electrical bladder stimulator for urinary incontinence
for use in children for the treatment of neurogenic bladder disease secondary to spina
bifida; a pulmonary valve for children under age 4 with absent or diseased valves; and an
extracorporeal immunoabsorption system for treatment of patients with hemophilia A and B
who have inhibitors to Factor VIII and IXcoagulation factors.
Part of meeting the Agencys mission to protect and promote the public health
involves effective management of FDAs limited resources. There are several FDAMA
provisions that reduce the Agencys workload in some areas so that those resources
can be reallocated to areas of the greatest public health risk. One such provision is the
device third party review program (section 210), which provides an alternative review
mechanism for low-to-moderate risk devices, thereby allowing FDA to target its scientific
review resources on higher-risk devices. There are currently 154 types of devices eligible
for review by third parties, and 13 accredited third party organizations. We have been
told that industry has made little use of this provision because CRDH has become so
efficient in its review of these devices.
Another provision that allows the Agency to focus its resources is section 213, device
user reporting. Prior to passage of FDAMA, all device user facilities were required to
report serious adverse events to FDA. Under FDAMA, FDA now has authority to establish a
sentinel system for user reporting, which would have a representative sample of hospitals
and other user facilities reporting serious adverse events to FDA. The Agency has already
conducted a pilot sentinel system, which was very successful. FDA is working to put an
expanded sentinel system in place. This initiative could ultimately ease the reporting
requirements for user facilities and enhance the value of reports the Agency receives.
More Efficient and Effective Regulatory Processes
FDAMA includes a number of provisions that streamline and expedite FDAs product
review processes by ensuring that sponsors know what is required, and by eliminating
unnecessary requirements. Clearly, PDUFA helps the Agency make decisions in a more timely
manner. At the same time, PDUFA and other aspects of the new statute ensure that FDA's
decisions are consistent and predictable. FDAs regulatory requirements are
clarified, providing industry with information about how to most effectively comply with
the applicable laws.
For example, both as part of the PDUFA agreement and as part of a separate FDAMA
requirement, the Agency is committed to meeting with drug sponsors to discuss and reach
agreement on the design and size of clinical trials. Any agreements reached can only be
changed under limited circumstances. Similarly, the device provisions provide for early
meetings with potential sponsors to focus on the type of valid scientific evidence needed
for device approval and to reach agreement on a study plan. These provisions, which
industry has been using extensively, are ensuring that industry knows up front what is
required, and, therefore, they will not waste time conducting unnecessary studies.
In addition, many provisions of the Modernization Act are premised on the principle
that regulatory requirements should not exceed what is required to protect and promote the
An example of matching regulatory requirements to meet public health risk is the
premarket notification provision in section 206. More than 60 Class II types of medical
devices have been exempted from pre-market notification requirements, enabling
manufacturers to get their products to market, and to patients who need them more rapidly.
The types of devices exempted include: clinical laboratory equipment and test kits, kidney
stone dislodgers, clinical thermometers, hospital beds, biofeedback devices and physical
rehabilitation devices. In addition, pursuant to this section, all but a limited number of
reserved Class I devices are exempt from 510(k) premarket notification as well.
FDAMA also streamlines the process for drug and device sponsors to make changes to
certain manufacturing processes. For example, the provision on scope of review in section
205, permits device manufacturers to notify FDA 30 days before instituting certain types
of manufacturing changes instead of submitting a premarket approval (PMA) supplement. This
means that the device manufacturer can often start marketing a device made from this new
process at least 5 months sooner than usually would have occurred before FDAMA. Industry
has already used this provision 80 times. The drug provision, which will go into effect on
November 21 of this year, permits drug manufacturers to make minor and moderate
manufacturing changes without prior approval of a supplemental application.
Section 205 of FDAMA, is similarly premised on the principle that regulatory
requirements should not exceed what is required to protect and promote the public health.
This provision requires FDA, in consultation with the product sponsor, to consider the
"least burdensome" means that will allow appropriate premarket development and
review of a device without unnecessary delays and expense to manufacturers. The
requirement to consider the least burdensome means applies to both existing statutory
paths to market: premarket notifications (510(k)s) and premarket approval applications
(including PMAs and Product Development Protocols). While FDAMA does not change the
standards for premarket review, it clarifies that the Agencys review is to focus on
information directly relevant to supporting the substantial equivalence or safety and
effectiveness of the medical device.
To foster a collaborative approach to the implementation of section 205 of FDAMA, CDRH
hosted a meeting with stakeholders on January 4, 1999, to solicit comments and suggestions
regarding the least burdensome approach to medical device development and evaluation. CDRH
heard formal presentations at that meeting and also received written comments. As a result
of communication with our stakeholders, FDA determined that the issue of when clinical
data would be required for devices was of the highest concern.
On September 1, 1999, FDA issued a draft guidance which describes how FDA may determine
the need for clinical data for device reviews. Additional tools that can be used to
facilitate the process of determining the least burdensome means to market will be
evaluated, prioritized, and developed as appropriate. Sponsors are encouraged to submit
their own proposals for the development of these additional tools at any time. The Agency
anticipates issuing future guidances on the least burdensome approach that are device
specific, as well as updating many of the current general and specific guidances in light
of these FDAMA provisions.
In the interim, FDA has been working to carry out the spirit of the least burdensome
requirement. For example, FDA reviewers approved a pediatric indication for a marketed
cardiac ablation without requiring a prospective clinical study because reviewers
determined that existing literature supported the devices safety and effectiveness
Another example of process improvements is the provision on data requirements in
section 118, which directs FDA to issue guidance on when abbreviated study reports may be
submitted in new drug applications (NDAs) and biologics license applications (BLAs), in
lieu of full reports. On September 13, 1999, FDA published a final guidance that describes
when abbreviated reports and synopses can be used to submit effectiveness data. This
guidance not only provides clarity, it should also ensure that industry is not submitting
more information than is required by the Agency.
Congress and FDA also recognized that industrys ability to rely on standards will
help to streamline the approval or clearance of medical devices. Under the
provision on device standards in section 204, CDRH recognized more than 500 consensus
standards that manufacturers may use to satisfy portions of device review requirements,
thus simplifying and expediting product review. Of these 500 recognized standards, over
100 were proposed by industry for recognition as a result of active solicitation by CDRH.
A few examples of consensus standards nominated by industry and recognized by CDRH
include: standards that can be used to describe and select the necessary biocompatibility
testing; most American Dental Association specifications for dental materials and devices;
and certain standards for safety requirements for electromedical equipment, covering over
30 individual standards on mechanical limits electrical safety considerations for
electrically powered devices.
At the same time, CDRH is trying to broaden the impact of the standards recognition
program mandated by FDAMA. CDRH is enlisting its stakeholders in setting priorities for
developing standards that can be recognized in the future and encouraging manufacturers to
incorporate recognized standards as part of their product specifications, which allows
extremely brief product descriptions, and thus, less lengthy 510(k)s.
In addition, FDAMA has helped to streamline the processes for submissions from industry
by codifying the modernization of certain biologics regulations. FDA recently issued a
final rule to implement the modernization of regulations provision in section 123, which
permits manufacturers to make a single submission for a biologics license, instead of
separate applications for the establish license and the product license. When as part of
FDAs Reinventing Government efforts first proposed to streamline the biologics
application process, industry representatives indicated that the change would result in
considerable savings of time and money. Since the implementation of the single
application/single license approach for specified products, industry representatives have
confirmed this to be the case.
While many of the provisions in the Modernization Act are designed to facilitate
agreement between FDA and industry on regulatory requirements, inevitably, there will be
disputes that remain. Section 404, the provision on dispute resolution requires the Agency
to clarify the processes for resolving scientific disagreements, including requests for
advisory panel review. While our existing regulations and procedures have worked well to
resolve many disagreements, the Agency is taking steps to enhance its dispute resolution
First, the Agency revised section 10.75 to clarify the availability of review of
scientific disputes by an advisory panel. CDRH created a medical devices dispute
resolution panel, and issued a draft guidance that describes how that panel will be used
to resolve scientific disputes. CDRH also issued a general guidance document that provides
an overview of all of the Centers dispute resolution processes. CDER and CBER have
developed guidance to explain their processes as well.
Open, Transparent Processes and Collaboration
As I stated in the beginning of my testimony, open and transparent Agency processes
provide consumers and industry with confidence in the Agencys decisions. For, as the
adage goes, "Only the wearer knows where the shoe pinches." We have worked to
ensure that everyone affected by the Agencys actions has a voice, and that each
voice is heard. While all of these voices can sometimes create a cacophony, we have found
that the amount of consumer confidence engendered by this open discourse is well worth the
FDAMA has contributed significantly to the Agencys effort to collaborate, and use
open, transparent processes that are credible and reliable. For example, section 406(b) of
the Modernization Act directs the Agency to consult with our constituencies to assure that
we fulfill our statutory mandates and that we communicate clearly with our stakeholders.
We have held a series of meetings over the last year, during which we have listened to
those outside the Agency. We hosted a national interactive videoconference that was
simulcast to interested parties in 8 different cities. During our national broadcast, we
had senior staff at each of the locations so a more focused communication could be held
with members of consumer groups and the regulated industry in these areas of the country.
During these meetings, we received useful feedback on the Agencys performance, as
well as constructive suggestions as to how the Agency can continue to improve. We are
currently reviewing each and every comment received, and are now planning another round of
these very important dialogues this spring.
FDAMA also includes both drug and device provisions that encourage open communication.
These provisions require FDA to meet with sponsors to discuss the kinds of studies that
would be needed for approval. This ensures that sponsors do not waste their time and
resources conducting studies that are ultimately unnecessary or inadequate. In addition,
there are requirements in the device provisions that permit sponsors to request a meeting
100 days after submission of a PMA. This meeting is intended to apprise the sponsor of
potential deficiencies with the application, and give the sponsor an opportunity to
resolve those problems as early as possible.
Finally, FDA has held countless public meetings to discuss implementation of specific
provisions. For example, CDER and CBER have held several public meetings on implementation
of certain provisions. These include, four public meetings on the implementation of the
positron emission tomography (PET) provisions, and three public meetings on the
As you can see, the Agency has been fully committed to implementation of FDAMA.
However, even as we have been devoting time, energy, and resources to this effort, we have
continued to meet the publics demands regarding our myriad other responsibilities.
Such responsibilities include: protecting the safety of the nations food supply and
blood supply, reviewing new cutting-edge food additives to ensure their safety, speeding
our reviews of new generic drugs and medical devices (neither of which are covered by user
fees) and developing a comprehensive regulatory strategy for dietary
supplementswhich involves the implementation of another complex statute.
I am delighted to be back at the Agency, and to have an opportunity to be involved in
the leadership and management of the implementation of such an important piece of
legislation. I am proud of the work that the Agency has done in fulfilling our commitment
to Congress and to the American people, and I hope that you share this sentiment. Thank
you for the opportunity to be here today.