prapharmacogeno gui ss

SUPPORTING STATEMENT

Guidance for Industry on Pharmacogenomic Data Submissions

OMB Control Number 0910-0557

Docket Number 2007N-0317

A. Justification

1. Circumstances of Information Collection

This information collection approval request is for a Food and Drug Administration (FDA) guidance for industry entitled “Pharmacogenomic Data Submissions.” The guidance provides recommendations to sponsors submitting or holding INDs, NDAs, or BLAs on what pharmacogenomic data should be submitted to the agency during the drug development process. Sponsors holding and applicants submitting INDs, NDAs, or BLAs are subject to FDA requirements for submitting to the agency data relevant to drug safety and efficacy (§§ 312.22, 312.23, 312.31, 312.33, 314.50, 314.81, 601.2, and 601.12). The guidance interprets FDA regulations for IND, NDA, or BLA submissions, clarifying when the regulations require pharmacogenomics data to be submitted and when the submission of such data is voluntary. The pharmacogenomic data submissions described in the guidance that are required to be submitted to an IND, NDA, BLA, or annual report are covered by the information collection requirements under parts 312, 314, and 601 (21 CFR parts 312, 314, and 601) and are approved by OMB under control numbers 0910-0014 (part 312—INDs); 0910-0001 (part 314--NDAs and annual reports); and 0910-0338 (part 601—BLAs).

The guidance distinguishes between pharmacogenomic tests that may be considered valid biomarkers appropriate for regulatory decisionmaking, and other, less well developed exploratory tests. The submission of exploratory pharmacogenomic data is not required under the regulations, although the agency encourages the voluntary submission of such data.

The guidance describes the voluntary genomic data submission (VGDS) that can be used for such a voluntary submission. The guidance does not recommend a specific format for the VGDS, except that such a voluntary submission be designated as a VGDS. The data submitted in a VGDS and the level of detail should be sufficient for FDA to be able to interpret the information and independently analyze the data, verify results, and explore possible genotype-phenotype correlations across studies. FDA does not want the VGDS to be overly burdensome and time-consuming for the sponsor.

2. Purpose and Use of Information

The guidance is intended to facilitate scientific progress in the field of pharmacogenomics and to facilitate the use of pharmacogenomic data in informing regulatory decisions. The guidance provides recommendations to sponsors holding INDs, NDAs, and BLAs on what pharmacogenomic data to submit to the agency during the drug development process, the format of submissions, and how the data will be used in regulatory decision making.

3. Use of Improved Information Technology

In the Federal Register of December 11, 2003, FDA issued a final rule amending FDA regulations governing the format in which certain labeling is required to be submitted for review with NDAs, certain BLAs, ANDAs, supplements, and annual reports. The final rule requires the electronic submission of the content of labeling (i.e., the content of the package insert or professional labeling, including all text, tables, and figures) in NDAs, certain BLAs, ANDAs, supplements, and annual reports electronically in a form that FDA can process, review, and archive.

The following guidances for industry are among those that have been developed to improve the use of information technology in the submission of marketing applications for human drugs and related reports:

• "Providing Regulatory Submissions in Electronic

Format--NDAs" (January 28, 1999). This guidance provides information on how to submit a complete archival copy of an NDA in electronic format and applies to the submission of original NDAs as well as to the submission of supplements and amendments to NDAs.

• "Providing Regulatory Submissions in Electronic

Format--General Considerations" (January 28, 1999). This guidance includes a description of the types of electronic file formats that the agency is able to accept to process, review, and archive electronic documents. The guidance also states that documents submitted in electronic format should enable the user to: (1) Easily view a clear and legible copy of the information; (2) print each document page by page while maintaining fonts, special orientations, table formats, and page numbers; and (3) copy text and images electronically into common word processing documents.

• “Providing Regulatory Submissions to the Center for

Biologics Evaluation and Research (CBER) in Electronic Format” (November 12, 1999). This guidance provides information to assist applicants in submitting documents in electronic format for review and archive purposes as part of a BLA, product license application (PLA), or establishment license application (ELA).

• "Providing Regulatory Submissions in Electronic Format-—Prescription Drug Advertising and Promotional Labeling" (January 31, 2001). This draft guidance discusses issues related to the electronic submission of advertising and promotional labeling materials for prescription drug and biological products.

• "Providing Regulatory Submissions in Electronic Format-—ANDAs" (June 27, 2002). This guidance discusses issues related to the electronic submission of ANDAs and supplements and amendments to those applications.

• "Providing Regulatory Submissions in Electronic Format-—Annual reports for NDAs and ANDAs" (August 2003). This guidance discusses issues related to the electronic submission of annual reports for NDAs and ANDAs.

• "Providing Regulatory Submissions in Electronic Format-—Postmarketing Periodic Adverse Drug Experience Reports" (June 2003). This guidance discusses general issues related the electronic submission of postmarketing periodic adverse drug experience reports for NDAs, ANDAs, and BLAs.

• "Providing Regulatory Submissions in Electronic Format-—Human Pharmaceutical Product Applications and Related Submissions" (August, 2003). This draft guidance discusses issues related to the electronic submission of ANDAs, BLAs, INDs, NDAs, master files, advertising material, and promotional material.

• "Providing Regulatory Submissions in Electronic Format-—General Considerations" (October 2003). This draft guidance discusses general issues common to all types of electronic regulatory submissions.

• "Providing Regulatory Submissions in Electronic Format-—Content of Labeling" (February 2004). This draft guidance discusses issues related to the submission of the content of labeling in electronic format for marketing applications for human drug and biological products.

These guidance documents are available at FDA's web

site http://www.fda.gov/cder/guidance/index.htm.

4. Efforts to Identify Duplication

The information collection requested under the guidance does not duplicate any other information collection.

5. Involvement of Small Entities

Although new drug development is typically an activity completed by large multinational drug firms, the information collection requested under the guidance applies to small as well as large companies. Under the Regulatory Flexibility Act, FDA regularly analyzes regulatory options that would minimize any significant impact on small entities. FDA also assists small businesses in complying with regulatory requirements.

6. Consequences If Information Collected Less Frequently

Sponsors holding INDs, NDAs, and BLAs would not be provided essential guidance on what pharmacogenomic data to submit to the agency during the drug development process, the format of submissions, and information on how the data will be used in regulatory decision making.

7. Consistency with the Guidelines in 5 CFR 1320.5(d)(2)

This guidance contains no inconsistency with the guidelines in 5 CFR 1320.5(d)(2).

8. Consultation Outside the Agency

In the Federal Register of August 21, 2007 (72 FR 46636), FDA published a notice requesting comment on the voluntary genomic data submissions. We received one comment which requested clarification of how the confidential information received in a VGDS will remain outside the public domain and not end up being cited in a publicly posted submission review. FDA response: Information received as part of a VGDS not to be used for regulatory decision-making and received in confidence is covered by the same confidentiality levels of INDs, NDAs, and BLAs. There is no publicly posted submission review associated with the data in a VGDS, and release of information associated with a VGDS is exclusively up to the sponsor of the VGDS and not to FDA.

9. Remuneration of Respondents

FDA has not provided and has no intention to provide any payment or gift to respondents under this guidance.

10. Assurance of Confidentiality

Confidentiality of the information submitted under this guidance is protected under 21 CFR 312.130 and 314.430 and under 21 CFR part 20. The unauthorized use or disclosure of trade secrets required in applications is specifically prohibited under Section 310(j) of the Act.

11. Questions of a Sensitive Nature

There are no questions of a sensitive nature.

12. Estimates of Annualized Hour Burden

FDA has estimated the burden of preparing a voluntary submission described in the guidance that should be designated as a VGDS. Based on FDA's experience with this guidance over the past few years, and on FDA’s familiarity with sponsors' interest in submitting pharmacogenomic data during the drug development process, FDA estimates that approximately 8 sponsors will submit approximately 10 VGDSs and that, on average, each VGDS will take approximately 50 hours to prepare and submit to FDA.

Table 1.--Estimated Annual Reporting Burden¹

	Number of Respondents	Number of Responses per Respondent	Total Annual Responses	Hours per Response	Total Hours
Voluntary Genomic Data Submissions	8	1.25	10	50	500

¹ There are no capital costs or operating and maintenance costs associated with this collection.

13. Estimates of Annualized Cost Burden to Respondents

FDA has estimated an average industry wage rate of $50.00 per hour for preparing and submitting the information collection under this guidance. Using the averaged wage rate of $50.00 per hour, and multiplied times the total hour burden estimated above, the total cost burden to respondents is $25,000 (500 x $50).

14. Estimates of Annualized Cost Burden to the Government

FDA estimates that the review of the VGDSs by FDA staff would require approximately 3 FTEs. Based on a cost of approximately $250,000 per FTE, FDA estimates the cost to be $750,000.

15. Changes In Burden

Based on our experience with the submission of VGDSs under this guidance over the past few years, the number of annual responses has been reduced from 80 to 10. In addition, we have reduced the hours per response from 80 hours to 50 hours.

16. Time Schedule, Publication, and Analysis Plans

There are no publications.

17. Displaying of OMB Expiration Date

The agency is not seeking to display the expiration date for

OMB approval of the information collection.

18. Exception to the Certification Statement - Item 19

There are no exceptions to the certification statement

identified in Item 19, "Certification for Paperwork Reduction Act

Submission," of OMB Form 83-I.

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