2010-6173. Agency Information Collection Activities; Proposed Collection: Comment Request: Guidance for Industry Entitled Hypertension Indication: Drug Labeling for Cardiovascular Outcome Claims

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) is announcing an opportunity for public comment on the proposed collection of certain information by the agency. Under the Paperwork Reduction Act of 1995 (the PRA), Federal agencies are required to publish notice in the Federal Register concerning each proposed collection of information, and to allow 60 days for public comment in response to the notice. This notice solicits comments on the information collection associated with the guidance “Hypertension Indication: Drug Labeling for Cardiovascular Outcome Claims,” which is intended to assist applicants in developing labeling for outcome claims for drugs that are indicated to treat hypertension.

DATES:

Submit written or electronic comments on the collection of information by May 21, 2010.

ADDRESSES:

Submit electronic comments on the collection of information to http://www.regulations.gov. Submit written comments on the collection of information to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT:

Elizabeth Berbakos, Office of Information Management, Food and Drug Administration, 1350 Piccard Dr., PI50-400B, Rockville, MD 20850, 301-796-3792, [e-mail]

SUPPLEMENTARY INFORMATION:

Under the PRA (44 U.S.C. 3501-3520), Federal agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of information that they conduct or sponsor. “Collection of information” is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes agency requests or requirements that members of the public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 60-day notice in the Federal Register concerning each proposed collection of information, before submitting the collection to OMB for approval. To comply with this requirement, FDA is publishing notice of the proposed collection of information set forth in this document.

With respect to the following collection of information, FDA invites comments on these topics: (1) Whether the proposed collection of information is necessary for the proper performance of FDA's functions, including whether the information will have practical utility; (2) the accuracy of FDA's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology.

Guidance for Industry entitled “Hypertension Indication: Drug Labeling for Cardiovascular Outcome Claims” 21 CFR 201.56 and 201.57—(OMB Control Number 0910—New)

This guidance is intended to assist applicants in developing labeling for outcome claims for drugs that are indicated to treat hypertension. With few exceptions, current labeling for antihypertensive drugs includes only the information that these drugs are indicated to reduce blood pressure; the labeling does not include information on the clinical benefits related to cardiovascular outcomes expected from such blood pressure reduction. However, blood pressure control is well established as beneficial in preventing serious cardiovascular events, and inadequate treatment of hypertension is acknowledged as a significant public health problem. FDA believes that the appropriate use of these drugs can be encouraged by making the connection between lower blood pressure and improved cardiovascular outcomes more explicit in labeling. The intent of the guidance is to provide common labeling for antihypertensive drugs except where differences are clearly supported by clinical data. The guidance encourages applicants to submit labeling supplements containing the new language.

In the Federal Register of March 13, 2008 (73 FR 13546), FDA published the draft guidance entitled “Hypertension Indication: Drug Labeling for Cardiovascular Outcome Claims.” The draft guidance contained no information collection subject to OMB review under the PRA. The final guidance, however, contains two new provisions that are subject to OMB review and approval under the PRA, and one new provision that would be exempt from OMB review. Under the PRA, FDA must first obtain OMB approval for this information collection before we may issue the final guidance.

(1) Section IV.C of the guidance requests that the CLINICAL STUDIES section of the Full Prescribing Information of the labeling should include a summary of placebo- or active-controlled trials showing evidence of the specific drug's effectiveness in lowering blood pressure. If trials demonstrating cardiovascular outcome benefits exist, those trials also should be summarized in this section. Table 1 in section V of the guidance contains the specific drugs for which the FDA has concluded that such trials exist. If there are no cardiovascular outcome data to cite, one of the following two paragraphs should appear:

“There are no trials of [DRUGNAME] or members of the [name of pharmacologic class] pharmacologic class demonstrating reductions in cardiovascular risk in patients with hypertension,” or “There are no trials of [DRUGNAME] demonstrating reductions in cardiovascular risk in patients with hypertension, but at least one pharmacologically similar drug has demonstrated such benefits.”

In the latter case, the applicant's submission generally should refer to table 1 in section V of the guidance. If the applicant believes that table 1 is incomplete, it should submit the clinical evidence for the additional information to Docket No. FDA-2008-D-0150. The labeling submission should reference the submission to the docket. FDA estimates that no more than 1 submission to the docket will be made annually from 1 company, and that each submission will take approximately 10 hours to prepare and submit. Concerning the recommendations for the CLINICAL STUDIES section of the Full Prescribing Information of the labeling, FDA regulations at §§ 201.56 and 201.57 (21 CFR 201.56 and 201.57) require such labeling, and the information collection associated with these regulations is approved by OMB under OMB Control Number 0910-0572.

(2) Section VI.B of the guidance requests that the format of cardiovascular outcome claim prior approval supplements submitted to FDA under the guidance should include the following information:

1. A statement that the submission is a cardiovascular outcome claim supplement, with reference to the guidance and related Docket No. FDA-2008-D-0150

2. Applicable FDA forms (e.g., 356h, 3397)

3. Detailed Table of Contents

4. Revised labeling:

a. Include draft revised labeling conforming to the requirements in §§ 201.56 and 201.57

b. Include marked-up copy of the latest approved labeling, showing all additions and deletions, with annotations of where supporting data (if applicable) are located in the submission

FDA estimates that approximately 70 cardiovascular outcome claim supplements will be submitted annually from approximately 30 different companies, and that each supplement will take approximately 4 hours to prepare and submit. The guidance also recommends that other labeling changes (e.g., the addition of adverse event data) should be minimized and provided in separate supplements, and that the revision of labeling to conform to §§ 201.56 and 201.57 may require substantial revision to the ADVERSE REACTIONS or other labeling sections.

(3) Section VI.C of the guidance states that applicants are encouraged to include the following statement in promotional materials for the drug.

“[DRUGNAME] reduces blood pressure, which reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals.”

The inclusion of this statement in the promotional materials for the drug would be exempt from OMB review based on 5 CFR 1320.3(c)(2), which states that “The public disclosure of information originally supplied by the Federal government to the recipient for the purpose of disclosure to the public is not included * * * ” within the definition of “collection of information.”

FDA requests public comments on the information collection provisions described previously and set forth in the following table:

FDA estimates the burden of this collection of information as follows:

Estimated Annual Reporting Burden

	Number of Respondents	Number of Responses per Respondent	Total Annual Responses	Hours Per Response	Total Hours
Submission to Docket Number FDA-2008-D-0150	1	1	1	10	10
Cardiovascular Outcome Claim Supplement Submission	30	2.33	70	4	280
Total					290

Dated: March 16, 2010.

Leslie Kux,

Acting Assistant Commissioner for Policy.