0014 INDs SSA AUG 2023 to add ICH Guidance REV

UNITED STATES FOOD AND DRUG ADMINISTRATION

Investigational New Drug Regulations

OMB Control No. 0910-0014 – Revision

SUPPORTING STATEMENT

Part A: Justification:

1. Circumstances Making the Collection of Information Necessary

This information collection supports implementation of provisions of section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355) and of the licensing provisions of the Public Health Service Act (42 U.S.C. 201 et seq.) that govern investigational new drugs and investigational new drug applications (IND). Implementing regulations are found in part 312 (21 CFR part 312) and provide for the issuance of guidance documents under 21 CFR 10.115 to assist persons in complying with the applicable requirements (see § 312.145). The information collection applies to all clinical investigations subject to section 505 of the FD&C Act.

We are revising the information collection to account for activities associated with recommendations found in the guidance document entitled E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1) (March 2018), currently approved in OMB control number 0910-0843. The guidance is intended to facilitate implementation of improved and efficient approaches to clinical trial design, including conduct, oversight, recording, and reporting. The recommendations in the guidance help us ensure that sponsors of clinical trials are adhering to requirements prescribed in Food and Drug Administration (FDA) regulations regarding new drug applications (NDA) (21 CFR part 312), INDs (21 CFR part 314), and biological licensing applications (BLA) (21 CFR part 601). The guidance document is available for download from our website at https://www.fda.gov/media/93884/download.

We are therefore requesting OMB approval to revise the information collection accordingly, and as discussed in this supporting statement.

2. Purpose and Use of the Information Collection

This information collection provides a means for sponsors of clinical trials involving human drugs and biological products to implement improved and more-efficient approaches to manage quality throughout all stages of the clinical trial process while continuing to ensure the protection of human subjects and the reliability of trial results. The recommendations of the guidance assist respondents with developing and implementing a quality management system while at the same time help us oversee sponsors’ responsibilities to ensure adequate protection of the rights, welfare, and safety of human subjects and the quality and integrity of the resulting data submitted to us.

3. Use of Improved Information Technology and Burden Reduction

We encourage electronic submission of the information required under parts 312, 314, and 601 and have developed several guidance documents describing the process for submitting information to us in electronic format. These guidance documents and others are available on our website at https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.

4. Efforts to Identify Duplication and Use of Similar Information

We are unaware of duplicative information collection. This consolidation request is based on a review of our active inventory and information collection associated with recordkeeping for developing and implementing a system to manage quality throughout all stages of the clinical trial process, and the reporting associated with describing the quality management approach implemented in the trial and summarizing important deviations from the predefined quality tolerance limits and remedial actions taken in the clinical study report. Upon OMB approval of the information collection request, we intend to discontinue OMB control number 0910-0843.

5. Impact on Small Businesses or Other Small Entities

Information collection recommendations found in the guidance apply to both small and large businesses. We routinely aid small businesses in complying with Agency requirements through its Regional Small Business Representatives and through the scientific and administrative staffs within the Agency. We have provided a Small Business Assistance on the Agency’s website at https://www.fda.gov/industry/small-business-assistance.

6. Consequences of Collecting the Information Less Frequently

We believe the recommended reporting and recordkeeping schedules found in the guidance represent minimal burden on respondents. Less frequent collection might undermine important oversight regarding implementation of clinical trials.

7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5

This information collection is consistent with the requirements of 5 CFR 1320.5.

8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the Agency

In accordance with 5 CFR 1320.8(d), we published a 60-day notice for public comment in the Federal Register on April 11, 2023 (88 FR 21682). No comments were received.

9. Explanation of Any Payment or Gift to Respondents

No remuneration is associated with the information collection.

10. Assurance of Respondent Privacy and Confidentiality

This ICR does not collect personally identifiable information (PII) or information of a personal nature. This information collection supports the development of a quality management system and reporting of this system to FDA-time estimates including the time to review instructions, search existing data sources, gather the data needed, and complete and review the information collection. Because neither FDA nor any party acting on behalf of the agency collects PII, the ICR is not subject to the Privacy Act of 1974 and the requirements of the Privacy Act such as displaying a Privacy Act Statement on a collection form do not apply.

Under the Freedom of Information Act (FOIA) (5 U.S.C. 552), the public has broad access to government documents. However, FOIA provides certain exemptions from mandatory public disclosure of government records (5 U.S.C. 552(b)(1-9)). FDA will make the fullest possible disclosure of records to the public, consistent with the rights of individuals to privacy, the property rights of persons in trade and confidential commercial or financial information.

11. Justification for Sensitive Questions

There are no questions of a sensitive nature associated with the information collection.

12. Estimates of Annualized Burden Hours and Costs

12a. Annualized Hour Burden Estimate

Table 1 -- Estimated Annual Recordkeeping¹

§ 312.145: Guidance Documents; Recommendations in ICH E6(R2) Good Clinical Practice	No. of Respondents	No. of Responses per Respondent	Total Annual Responses	Average Burden per Response	Total Hours
Section 5.0.7. Risk Reporting--Describing the Quality Management Approach Implemented in a Clinical Trial and Summarizing Important Deviations From the Predefined Quality Tolerance Limits and Remedial Actions Taken in the Clinical Study Report	1,880	3.9	7,362	3	22,082
Section 5 Quality Management (including sections 5.0.1 to 5.0.7) - Developing a Quality Management System	1,880	1	1,880	60	112,800
TOTAL			9,242		138,744

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

Respondents to the collection of information are sponsors of clinical trials of human drugs. Based on IND and NDA submission data, including submissions to both FDA’s Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research, we estimate there are 1,880 respondents to the information collection. We assume the risk reporting recommendations and associated records discussed in section 5 of the guidance document requires 3 hours to complete, as reflected in table 1 row 1. In table 1, row 2, we account for burden associated with the development of a quality management system and associated recordkeeping also discussed in section 5 of the guidance document. We assume it will take respondents 60 hours to develop and implement each quality management system, as recommended. These estimates are based on our past experiences with INDs, BLAs and NDAs submitted to FDA.

12b. Annualized Cost Burden Estimate

Using a fully loaded wage rate of $156 per hour for regulatory personnel that would be engaged in the information collection and multiplying that by the total number of hours (138,744), we calculate the annual cost to respondents for the information collection as

$21,644,064.

13. Estimates of Other Total Annual Costs to Respondents and/or Recordkeepers/Capital Costs

There are no capital expenditures or start-up, operating, or maintenance costs associated with this information collection.

14. Annualized Cost to the Federal Government

We estimate it takes approximately 30 minutes to review each submission recommended in the guidance. Assuming a cost of $325,348 per one full time equivalents (salary plus overhead, full-time 40-hour week) divided by the total number of hours worked (2080 hours) per year, the fully loaded wage rate is $156 per hour. Using a fully loaded wage rate of $156 per hour for an FDA reviewer multiplied by the number of submissions received annually (10,528), we calculate the annualized cost to the Federal government is $821,184.

15. Explanation for Program Changes or Adjustments

By including burden previously accounted for under control no. 0910-0843, we have adjusted our estimate to include an additional 9,242 responses and 138,744 hours annually. This increase is reflected in the IC element entitled, “CDER: 312 Subpart F - Miscellaneous provisions including import & export requirements and foreign clinical studies and issuance of guidance to help comply with regulatory requirements (312.145),” accompanied by the subject guidance.

16. Plans for Tabulation and Publication and Project Time Schedule

There are no publications or other schedules.

17. Reason(s) Display of OMB Expiration Date is Inappropriate

We display the OMB expiration date as required by 5 CFR 1320.5. Upon OMB approval we intend to discontinue ICR 0910-0843 and update the control number and expiration date accordingly.

18. Exceptions to Certification for Paperwork Reduction Act Submissions

There are no exceptions to the certification statement.