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Daily Rules, Proposed Rules, and Notices of the Federal Government

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2001D-0432]

Guidance for Industry on Orally Inhaled and Intranasal Corticosteroids: Evaluation of the Effects on Growth in Children; 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 "Orally Inhaled and Intranasal Corticosteroids: Evaluation of the Effects on Growth in Children." This guidance provides recommendations regarding the design, conduct, and evaluation of clinical trials to assess the effects of orally inhaled and intranasal corticosteroids on growth in children. For this class of drug products, measurement of growth is considered a sensitive surrogate of, and an important sentinel for, the potential to cause systemic effects. Growth studies designed and carried out following the recommendations in this guidance can provide adequate and well-controlled data that are consistent among drug products and can be included in product labeling. This guidance finalizes the draft guidance published on November 6, 2001.
DATES: Submit written or electronic comments on agency guidances at any time.
ADDRESSES: Submit written requests for single copies of this guidance to the Division of Drug Information (HFD-240), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. Send one self-addressed adhesive label to assist that office in processing your requests. Submit written comments on the guidance to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments tohttp://www.fda.gov/dockets/ecomments. See theSUPPLEMENTARY INFORMATIONsection for electronic access to the guidance document.
FOR FURTHER INFORMATION CONTACT: Peter Starke, Center for Drug Evaluation and Research (HFD-7), Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, rm. 3300, Silver Spring, MD 20993-0002, 301-796-2300.
SUPPLEMENTARY INFORMATION: I. Background

FDA is announcing the availability of a guidance for industry entitled “Orally Inhaled and Intranasal Corticosteroids: Evaluation of the Effects on Growth in Children.” This guidance provides recommendations for the design, conduct, and evaluation of clinical studies to assess the effects of orally inhaled and intranasal corticosteroids on linear growth (“growth study”). The guidance was developed by the Division of Pulmonary and Allergy Products in consultation with the Division of Metabolism and Endocrinology Products and the Office of Biostatistics to encourage the collection of evidence that can consistently and accurately describe the effects of intranasal and orally inhaled corticosteroids on growth velocity in children.

In July 1998, the Pulmonary and Allergy Drugs Advisory Committee and the Metabolic and Endocrine Drugs Advisory Committee were jointly convened to discuss the implications of findings in previous clinical studies that indicated that inhaled corticosteroids can, as a class of drug products, affect linear growth in pediatric patients. The joint committee concluded that data were sufficient to justify inclusion of a precautionary statement in the labeling for this class of drug products, but the data were inadequate to precisely determine the decrement in growth velocity resulting from the use of these drug products. Members of the joint committee recommended that companies filing new drug applications for all newly approved corticosteroid products conduct further studies, as post-approval phase 4 commitments, to assess the effects of nasally and orally inhaled corticosteroids on growth velocity in prepubertal children. On November 6, 2001 (66 FR 56109), FDA published for comment in theFederal Registera draft of this guidance.

Comments received from industry, professional societies, and consumer groups on the draft guidance have been taken into consideration in finalizing this guidance. Changes are based on thorough review of all comments received, growth studies submitted since publication of the draft guidance, and previously submitted growth data. Changes or updates were made to all sections of the guidance, and are briefly summarized here.

A new overview section and updated background and data analysis sections include a more thorough discussion of the objective of and the appropriate statistical comparisons for a growth study. These changes will affect future labeling for such studies. Recommendations for sample size calculations and primary and secondary “sensitivity” analyses have been reviewed and modified based on review of growth studies submitted since publication of the draft guidance as well as previously submitted data. The general study recommendations and protocol design sections include a discussion of the appropriate patient populations to be studied and modifications to recommendations for the inclusion and exclusion criteria, assessments of adherence, and spacer use.

This guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance represents the agency's current thinking on the evaluation of the effects of orally inhaled and intranasal corticosteroids on growth in children. 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 statutes and regulations.

II. Comments

Interested persons may submit to the Division of Dockets Management (seeADDRESSES) written or electronic comments on the draft guidance. Submit a single copy of electronic comments or two paper copies of any mailed comments, except that individuals may submit one paper copy. Comments are to be identified with the docket number found in brackets in the heading of this document. The draft guidance and received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

III. Electronic Access

Persons with access to the Internet may obtain the document at eitherhttp://www.fda.gov/cder/guidance/index.htmorhttp://www.fda.gov/ohrms/dockets/default.htm.

Dated: February 26, 2007. Jeffrey Shuren, Assistant Commissioner for Policy.