Statement by

Jane E. Henney, M.D.

Commissioner of Food and Drugs

Food and Drug Administration

before the

Committee on Health, Education, Labor and Pensions

United States Senate

October 21, 1999

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 Agency's 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 the law.

Over the past two years, FDA has worked diligently on implementation of this new statute, which touches nearly every facet of the Agency's 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 overstated-it 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 Agency's 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 those consumers.

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 FDA's 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 Act's benefits to the public health can be grouped in two categories: greater patient access to new medical products and more effective management of FDA's 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 Agency's 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 5 years later. FDA's 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 market-a 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 them.

Another FDAMA success story is the fast track provision in section 112. In the fast track provision, Congress codified FDA's 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 medical need.

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 evidence-including evidence from studies with surrogate endpoints. This allows us to make our risk/benefit determination both accurately and more rapidly than before.

Since the passage of the Modernization Act, we have granted fast track designation for a wide range of therapies-not 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, FDA's Center for Drug Evaluation and Research (CDER) had received 59 requests for fast track designation-41 were granted, 14 denied, and 4 are still pending. FDA's Center for Biologics Evaluation and Research (CBER) had received 34 requests-20 were granted, 10 denied, and 4 are still pending.

The approvals that have occurred under the fast track program demonstrate the Agency's successful implementation of expedited review. Since we began implementing this provision, we have approved four products-Herceptin, 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.

FDAMA's 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 Agency's 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 children's 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 drug's label, it is also important to get all of the information about a drug's 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 patient's 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 Agency's current procedures for this program, the statute ensures that this program will continue to provide expanded access to patients in the future.

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 IX-coagulation factors.

Part of meeting the Agency's mission to protect and promote the public health involves effective management of FDA's limited resources. There are several FDAMA provisions that reduce the Agency's 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 FDA's 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. FDA's 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 public health.

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 Agency's 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 device's safety and effectiveness in children.

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 industry's 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 FDA's 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 processes.

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 Center's 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 Agency's decisions. For, as the adage goes, "Only the wearer knows where the shoe pinches." We have worked to ensure that everyone affected by the Agency's 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 noise.

FDAMA has contributed significantly to the Agency's 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 Agency's 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 radiopharmaceuticals provisions.

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 public's demands regarding our myriad other responsibilities. Such responsibilities include: protecting the safety of the nation's 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 supplements-which 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.