Legislative Notice #31

July 22, 1997

Calendar No. 105

Reported from the Labor Committee on July 1, 1997. The Committee adopted a substitute amendment offered by Chairman Jeffords by a vote of 14 to 4. Voting nay were Senators Kennedy, Harkin, Bingaman, and Reed. S. Rept. 105-43, additional and minority views filed.

• Senate action on S. 830 may begin this week. Senator Kennedy has indicated he may object to proceeding to the bill, in which case, cloture votes can be anticipated. The House Commerce Committee is expected to report out legislation comparable to S. 830 prior to the August recess. [See page 6 of this Notice for Administration's views.]
• In addition to streamlining FDA procedures, S. 830 reauthorizes the Prescription Drug User Fee Act (PDUFA) of 1992, scheduled to expire October 1, 1997. PDUFA allows the FDA to levy user fees on pharmaceutical manufacturers in order to cover the costs of drug safety and efficacy reviews.
• The bill includes statutory language allowing manufacturers to give seriously ill patients (acting through a licensed physician) access to unapproved investigational drugs.
• As reported, S. 830 establishes "fast-track" approval (similar to the HIV/AIDS and cancer fast-track process) of new drugs for treatment of serious or life-threatening disease.
• The bill increases agency accountability by, among other things, requiring FDA to develop a plan to eliminate, by the year 2000, the backlog of products awaiting approval.
• The legislation also will allow food labels to include bona fide health claims; supplement agency resources and expertise by directing FDA to expand the use of accredited third-party review of new medical devices; and provide incentives for drug manufacturers to conduct pediatric studies and establish labeling standards with respect to a drug's health benefits for children.

Title I: Improving Patient Access

The bill establishes in statute the FDA's mission. In general, the legislation seeks to guarantee that the FDA will continue to protect the public against unsafe or ineffective products while providing a better balance in the law by ensuring timely access to safe and effective products.

Expanded Access to Investigational Therapies. The committee substitute contains language to greatly expand patient access to experimental medical treatments.

• Any person, acting through a licensed physician, may request access to an unapproved investigational drug or device (and any manufacturer may provide such a product) for the treatment of a serious illness for which there is not an effective, approved therapy.
• Only those products for which the manufacturer is already seeking FDA approval will be accessible under the program.

Expanded Humanitarian Use of Medical Devices. The bill eliminates impediments to the timely approval of (and access to) humanitarian devices for patient populations of less than 4,000 for whom no approved treatment of a disease is currently available.

• Specifically, it would allow a physician who has applied for a hospital review committee's approval to use such a device if the patient would suffer harm or death while waiting for approval from the committee.
• FDA will have 60 days to review the application. In addition, the FDA could no longer require a physician to seek re-approval unless the agency provides a written justification for doing so.

Title II: Increasing Access to Expertise and Resources

In order to promote interagency cooperation and to streamline FDA approval procedures, the bill provides for increased reliance on accredited academic institutions and outside research facilities in the FDA review process.

Contracts for Expert Review. The bill requires the FDA to enter into contracts with nongovernmental entities to review products or medical devices, if it is determined that doing so would improve the timeliness or quality of the review.

Program for Third-Party Accreditation. The FDA is required to expand its existing pilot program for third-party review of medical devices beyond the current 30 Class II products (out of a total of 850 low-risk, Class II products) to other low-risk products.

• Excludes long-term implants (e.g., pace-makers), life support devices, Class III products, as well as products with substantial importance in the prevention of impairment to human health.
• Upon request, the FDA must provide a sponsor of a medical device, who is seeking FDA approval, with a minimum of two accredited parties from which to choose for review of the sponsor's application. The sponsor would be responsible for the accredited party's compensation, but such arrangements would continue to be subject to agency scrutiny. This provision is designed to ensure agency access to additional resources and outside expertise without imposing user fees.

Global Harmonization. The Committee included language urging the Departments of Commerce and Health and Human Services to work toward the acceptance of mutual recognition agreements (MRAs) with the European Union on the regulation of drugs, medical devices, food, and food additives.

Title III: Improving Collaboration and Communications

In order to hold the FDA to its statutory 180-day limit to review applications for the approval of new drugs and devices, the Committee has included a number of provisions to streamline the review process.

Collaborative Determinations of Device Data Requirements. Upon the written request of a device sponsor, the FDA will be required to meet with the sponsor to determine the type of scientific evidence that is necessary to demonstrate the effectiveness of a device. Such determinations, once agreed to, are binding except where the public health warrants an exception.

• A collaborative review secretary is required to meet with the product sponsor within 100 days of receiving a complete premarket approval application (PMA), if requested in writing by the sponsor, to report on the status of the application and any deficiencies that may have arisen.

Title IV: Improving Certainty and Clarity of Rules

The bill makes a series of changes related to the classification, review, and approval of FDA-regulated products designed to ensure that the sponsors of new products face consistent and equitable regulatory requirements.

• Policy Statements. The bill requires FDA to convert from its current reliance on informal policy statements ("Good Guidance Practices" document) to regulation after two years.

• Data Requirements: The FDA will be permitted to use data from PMAs 6 years after approval to facilitate reclassification or review of other like applications.

• Product Classification. The bill requires that within 60 days of receiving a written request, the FDA must provide an applicant for premarket review with a written determination regarding the classification of the product.
• Labeling Claims. In making determinations to approve or deny an application, the FDA will be required to limit the evaluation of safety and effectiveness to those uses proposed in the product label if it is determined that the labeling is neither false nor misleading.
• Number of Required Clinical Investigations. The FDA is given discretion to approve drugs on the basis of one adequate and well-controlled clinical investigation and confirmatory evidence.

Title V: Improving Accountability

The bill seeks to ensure FDA performance of its statutory obligations by streamlining its review and inspection procedures and requiring greater public accountability. In achieving the latter, the Committee has included language requiring the FDA to eliminate its backlog of products awaiting final action by the year 2000.

Title VI: Better Allocation of Resources by Setting Priorities

As reported, the bill establishes a number of priorities on which the FDA is to focus.

• Approval of Fast Track Drugs. The bill directs the FDA to facilitate development and expedite approval of new drugs and biological products, to be known as "fast track drugs," that are intended to treat serious and life-threatening illnesses for which no approved therapy exists.
• Manufacturing Changes for Drugs and Biologics. New drugs that have undergone minor changes in the manufacturing process (established in the original application) may be distributed 30 days after the FDA has received a supplemental application from the sponsor, unless the applicant is notified that prior approval of the supplement is required.
• Food Contact Substances. The preapproval process for food contact substances (primarily packaging materials) is replaced with a simple notification requirement. Current law requires FDA preapproval of food contact substances, most of which pose little, if any, risk to human health.
• Health Claims for Food Products. The bill provides an alternative to the current standard and review process by allowing health claims in food labeling without FDA authorization, where such claims are based on information published by authoritative U.S. government scientific bodies such as the National Institutes of Health (NIH). However, health claims must be submitted to the FDA, along with the published information on which it is based, at least 120 days prior to marketing of the label.
• Pediatric Studies. The bill will provide a market incentive for drug manufacturers to conduct studies on the health benefits of new and existing drugs to children. If the FDA determines that a new (or already marketed drug) will produce health benefits in a pediatric population, and the manufacturer completes a study to that effect, then the manufacturer will be eligible for an additional six months of market exclusivity in that sale of that drug.

Title VII: Fees Relating to Drugs

• Prescription Drug User Fee Act of 1992 (PDUFA) Reauthorization. The bill reauthorizes PDUFA for an additional five years. The act requires the payment of user fees whenever a drug manufacturer submits an application for FDA review. S. 830 amends PDUFA to allow 75 percent of the fee (instead of the current 50 percent) to be refunded if FDA refuses to file an application.
• Exceptions to Payment of Fees. Three exceptions to the payment of fees are added: (1) applications for designated orphan drugs intended for the treatment of rare diseases; (2) application fees for pediatric drugs, other than those that are initial applications for approval in a pediatric population or applications which seek approval for use in both pediatric and adult populations; and (3) fees on applications which the manufacturer subsequently withdraws.
• Small Business Waiver. The FDA will grant a one-time waiver of the application fee to small businesses (fewer than 500 employees) that are submitting their first human drug application.
• Amount of Fees. CBO estimates that the FDA will collect $601 million in user fees over the five-year reauthorization period (FYs 1998-2002). The bill sets the "full fee" amount per application at $250,704 in FY 1998, increasing to $258,451 in FY 2002.

Title VIII: Miscellaneous

(See Committee report, beginning on page 96, for details on Title VIII provisions.)

At press time, no official "Statement of Administration Position" had been issued with respect to S. 830. Many of the earlier concerns with the bill (outlined in a June 11, 1997, letter from Health and Human Services Secretary Donna Shalala to Chairman Jeffords) have been resolved. A managers' substitute is likely to be offered during floor consideration of the bill to reflect language agreed upon by the Administration.

Although a number of issues raised in Committee (see Kennedy/Harkin amendments, page 12 of the Committee report) have been resolved since the bill was reported out, several additional amendments may yet be offered during floor consideration of S. 830, including:

Hutchison. Clinical Laboratory Improvement Act.

Mack/Frist. Off label use information for physicians.

Frist/Wellstone. To reauthorize clinical pharmacology programs at universities.

Durbin. Health claims on food labels.

Durbin. Third-party review.

Harkin. Alternative Medical Treatment Act.

Harkin. Supersede ongoing litigation on regulation of ultrasound contrast media.

McConnell. Food package labeling (possibility of two amendments).

Feinstein. Uniformity provisions.