[Federal Register: May 15, 1998 (Volume 63, Number 94)] [Notices] [Page 27093-27094] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr15my98-110] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. 97D-0100] Guidance for Industry on Providing Clinical Evidence of Effectiveness for Human Drugs and Biological Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled ``Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products.'' The purpose of this guidance is to clarify what clinical evidence of effectiveness should be provided in new drug applications, biological product license applications, and supplemental applications for new uses of drugs and biologics. The guidance is also intended to fulfill the requirements of certain provisions of the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). DATES: General comments on agency guidance documents are welcome at any time. ADDRESSES: An electronic version of this guidance is available via the Internet at http://www.fda.gov/cder/guidance/index.htm and at http:// www.fda.gov/cber/guidelines.htm. Submit written comments on this guidance to the Dockets Management Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, Rockville, MD 20857. Comments are to be identified with the docket number found in brackets in the heading of this document. FOR FURTHER INFORMATION CONTACT: Joseph P. Griffin, Center for Drug Evaluation and Research (HFD-5), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-594-5400. SUPPLEMENTARY INFORMATION: The draft guidance for industry entitled ``Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products'' (the draft guidance) was initially developed as part of an effort to get more information about valid uses of marketed drugs into the labeling of these drugs. Uncertainty on the part of the industry about the evidentiary requirements for demonstrating effectiveness for a supplemental indication was believed to be an obstacle to sponsors submitting applications for supplemental indications. The draft guidance was intended to clarify the amount and types of evidence that could be used to demonstrate effectiveness and thereby facilitate submission of additional supplemental applications. In the Federal Register of March 21, 1997 (62 FR 13650), FDA announced the availability of the draft guidance. The notice gave interested persons an opportunity to submit comments by May 20, 1997. On November 21, 1997, the President signed the Modernization Act (Pub. L. 105-115), which addressed both the standards for providing clinical evidence of effectiveness and the evidentiary requirements for supplemental applications. Section 115 of the Modernization Act amended the definition of substantial evidence in section 505(d) of the Federal Food, [[Page 27094]] Drug, and Cosmetic Act (the act) (21 U.S.C. 355(d)) to clarify that FDA, at its discretion, may make exception to the general requirement that there must be more than one adequate and well-controlled investigation to support an effectiveness determination. Section 115 of the Modernization Act provides in relevant part that ``[i]f the [agency] determines, based on relevant science, that data from one adequate and well-controlled clinical investigation and confirmatory evidence (obtained prior to or after such investigation) are sufficient to establish effectiveness, the [agency] may consider such data and evidence to constitute substantial evidence [of effectiveness].'' In clarifying the standard for substantial evidence, Congress acknowledged the agency's position that there have been major advances in the science and practice of clinical drug development since the effectiveness requirement was added to the act in 1962, and confirmed FDA's interpretation of the substantial evidence of effectiveness standard, as explained in the draft guidance document. In addition to the provision on the evidence standard, the Modernization Act included section 403, ``Approval of Supplemental Applications for Approved Products.'' Section 403(a) of the Modernization Act requires FDA to publish in the Federal Register, within 180 days of enactment, standards for the prompt review of supplemental applications for drugs and biological products. These standards are included in a guidance document for which a notice of availability is published elsewhere in this issue of the Federal Register. Section 403(b) of the Modernization Act requires that FDA, within 180 days of enactment, issue final guidances to clarify the requirements for, and facilitate the submission of data to support, the approval of supplemental applications for drugs and biologics. The guidance issued today fulfills this statutory requirement as it addresses the data requirements for both original drug and biological product applications and supplements to those applications. In addition, section 403(b)(1) of the Modernization Act requires that FDA provide guidance to ``clarify circumstances in which published matter may be the basis for approval of a supplemental application.'' Section III of the guidance describes the circumstances in which a sponsor may rely in part, or entirely, on published reports of studies to support approval of a supplemental application. Section 403(b)(2) of the Modernization Act requires that FDA provide guidance to ``specify data requirements that will avoid duplication of previously submitted data by recognizing the availability of data previously submitted in support of an original application.'' Section II of the guidance describes a range of circumstances in which existing data, whether or not previously submitted to an original application, may be used to support an application for a supplemental indication, thus permitting a sponsor to avoid developing unnecessary additional data. The agency received 13 submissions commenting on the draft guidance, including comments from pharmaceutical and biological products companies and their trade associations, individuals and organizations in academic medicine and clinical pharmacology, patient advocacy organizations, and a consumer. The response to the draft guidance was generally favorable. The guidance was viewed as a significant step forward by the agency in clarifying and better articulating its quantitative and qualitative evidentiary standards for evidence of effectiveness. Comments observed that the principles espoused were scientifically reasonable, practical, and appropriately flexible. The agency has considered all of the comments in making revisions to the guidance document. This guidance document is being issued as a Level 1 guidance consistent with FDA's good guidance practices (62 FR 8961, February 27, 1997). It represents the agency's current thinking on clinical evidence of effectiveness for human drug and biological products. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both. Submit written requests for single copies of the guidance for industry entitled ``Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products'' to the Drug Information Branch (HFD-210), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857; or the Office of Communication, Training and Manufacturers Assistance (HFM-40), Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852-1448. Please send one self-addressed adhesive label to assist the offices in processing your request. The document may also be obtained by mail by calling the CBER Voice Information System at 1-800-835-4709 or 301-827- 1800, or by fax by calling the CBER FAX Information System at 1-888- CBERFAX or 301-827-3844. Interested persons may at any time submit written comments on the guidance to the Dockets Management Branch (address above). Requests and comments should be identified with the docket number found in brackets in the heading of this notice. A copy of the guidance and received comments may be seen in the office above between 9 a.m. and 4 p.m., Monday through Friday. Dated: May 8, 1998. William B. Schultz, Deputy Commissioner for Policy. [FR Doc. 98-12901 Filed 5-14-98; 8:45 am] BILLING CODE 4160-01-F